Biomedical subjects
Publications and source records attributed to A Pinto.
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Viral meningitis is a common disease, most often benign and striking predominantly children. In 1997, there was an outbreak of viral meningitis in the North of Portugal and this pathology accounted for 496 admissions to the Infectious Diseases Department of S. João Hospital. The authors' aim was to determine the etiology of the cases of viral meningitis admitted to the S. João Hospital by, in a first phase, searching enterovirus and serology for mumps in a sample of 142 patients with symptoms, signs and cerebrospinal fluid (CSF) cytochemical abnormalities typical of viral meningitis, in the absence of any bacterial or fungal growth (in blood and/or CSF) and with negative soluble bacterial antigens in CSF. The enterovirus was detected by polymerase chain reaction (PCR) and, in a small number of cases, by shell vial culture. The diagnosis of mumps was made by the detection of specific IgM antibodies in serum, using an enzyme-linked immunosorbent assay. The diagnosis was reached in 70 patients (49.3%): 47 (33.1%) had mumps meningitis and 23 (16.2%) enterovirus infection (PCR positive in all; culture positive in only 2 cases). In 72 patients (50.7%), the agent was not identified. Although only two agents were searched for, the diagnosis was made in a high proportion of cases. The culture method used for the isolation of enterovirus was found to have a low sensitivity.
The present study investigated the possible role of nitric oxide (NO) in the development of the withdrawal contractures of guinea pig isolated ileum after acute activation of mu- and kappa-opioid receptors. After a 4-min in vitro exposure to morphine (mu-opioid receptor preferring, but not selective, agonist), [D-Ala2-N-methyl-Phe4-Gly5-ol-]enkephalin (DAMGO; highly selective mu-opioid receptor agonist), or trans(+/-)-3,4-dichloro-N-methyl-N-2(1-pyrrolidynyl)cyclohexyl-ben zeneacetamide (U50-488H; highly selective kappa-opioid receptor agonist), the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. L-N(G)-nitro arginine methyl ester (3-300 microM) injected 10 min before the opioid receptor agonists was able dose dependently to reduce the naloxone-induced contraction after exposure to mu- and kappa-opioid receptor agonists whereas D-N(G)-nitro arginine methyl ester at the same concentrations did not affect it. The inhibitory effect of L-N(G)-nitro arginine methyl ester on morphine, DAMGO and U50-488H withdrawal was dose dependently reversed by L-arginine (3-300 microM) but not by D-arginine. Finally, glyceryl trinitrate on its own (3-300 microM) significantly increased the naloxone-induced contraction after exposure to mu- and kappa-opioid receptor agonist and it was also able to reverse the inhibition of opioid withdrawal caused by L-N(G)-nitro arginine methyl ester. These results provide evidence that NO has a role in the development of opioid withdrawal and that mu- or kappa-opioid receptors are involved.
The pharmacological properties of voltage-dependent calcium channel (VDCC) subtypes appear mainly to be determined by the alpha1 pore-forming subunit but, whether P-and Q-type VDCCs are encoded by the same alpha1 gene presently is unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at motor nerve terminals that underlie muscle weakness in the autoimmune Lambert-Eaton myasthenic syndrome (LEMS). We first studied their action on changes in intracellular free Ca2+ concentration [Ca2+]i in human embryonic kidney (HEK293) cell lines expressing different combinations of human recombinant VDCC subunits. Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent reduction in the K+-stimulated [Ca2+]i increase in the alpha1A cell line but not in the alpha1B, alpha1C, alpha1D, and alpha1E cell lines, establishing the alpha1A subunit as the target for these autoantibodies. Exploiting this specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and observed a reduction in P-type current in Purkinje cells and both P- and Q-type currents in granule cells. These data are consistent with the hypothesis that the alpha1A gene encodes for the pore-forming subunit of both P-type and Q-type VDCCs.
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Thirty-eight patients with primary resistant or relapsing acute myeloid leukemia (AML) were treated with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). Median age was 41 (range 11-70). Sixteen patients had AML that was primary resistant to induction treatment, while 22 were relapsed, 11 after autologous bone marrow transplant (AuBMT), 8 less than 6 months from complete remission (CR) achievement, and 3 were second relapse from chemotherapy alone. Overall, 21 of 38 patients (55%) obtained CR. Age, sex, length of CR, and interval between autoBMT and FLAG administration did not significantly influence the CR rate. On the contrary, a normal karyotype at diagnosis was significantly related to a better outcome. There were 4 induction deaths (10%), due to fungal infection in 2 patients and hemorrhagic complications in the remaining two. All patients experienced profound cytopenia. Median time to neutrophil (>500/microl) recovery was 21 days, while a platelet count >20,000/microl was reached after 23 days. The median period of hospitalization was 31 days. The nonhematological toxicity was mild, mainly consisting of mucositis. There were 17 documented infections and 17 episodes of fever of unknown origin. Following CR achievement, 6 patients received autoBMT, 3 alloBMT, 2 high-dose arabinosil-cytosine, and 2 are on a waiting list for transplantation procedure. We conclude that FLAG is an effective and well-tolerated regimen for refractory or recurrent AML, mainly useful for patients to be admitted to bone marrow transplantation.
The psychometric properties and validity of the Reasons for Living (RFL) Inventory were examined in a sample of psychiatrically hospitalized adolescents (n = 253), aged 13 to 18 years, identified as suicide ideators, suicide attempters, and psychiatric controls. Confirmatory factor analysis suggested that the original RFL factors did not provide a good fit; exploratory factor analysis identified five factors, of which three were identical with the original RFL factors. Factor scores differentiated suicidal from non-suicidal adolescents and attempters from ideators. Correlational analyses indicated that RFL factors were associated with suicidal ideation, depression, and hopelessness, and predicted unique variance in suicidal ideation over that accounted for by depression and hopelessness. Our findings provide support for the RFL as a sound measure for clinical and research assessment in adolescents.
Hodgkin's disease (HD) is a peculiar type of human malignant lymphoma characterized by a very low frequency of tumor cells, the so called Hodgkin and Reed-Sternberg (H-RS) cells, embedded in a hyperplastic background of non-neoplastic (reactive) cells recruited and activated by H-RS cells-derived cytokines. H-RS cells can be functionally regarded as antigen-presenting cells (APC) able to elicit an intense, but anergic and ineffective, T-cell mediated immune response along with a hyperplastic inflammatory reaction which involves several cell types including T- and B-cells, neutrophils, eosinophils, plasma cells, fibroblasts and stromal cells. In tissues involved by HD, malignant H-RS cells and their reactive neighboring cells are able to cross-talk via a complex network of cytokine- and cell contact-dependent interactions. As a result of such interactions, mediated by specific surface receptors and adhesion molecules on both tumor and non-neoplastic cells, H-RS cells may receive several proliferative and anti-apoptotic signals favoring the cellular expansion and tumor cell survival in HD. The ineffective T-cell immune response elicited by the abnormal APC function of H-RS cells may further contribute to the biologic and clinical progression of HD. Innovative therapeutic strategies aimed at blocking the pathways of dysregulated cellular cross-talk among H-RS cells and bystander reactive cell populations might be beneficial in the treatment of HD patients.
Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) has been proposed as a potential tracer in patients with multiple myeloma (MM). The aims of this study were to evaluate the incidence of various patterns of diffuse 99mTc-MIBI uptake in patients with MM, to assess their relationship with clinical status and stage of disease, and to try to clarify the meaning of the diffuse bone marrow uptake of 99mTc-MIBI. Thirty-nine consecutive patients with MM were studied. Twenty-nine of these patients had active disease (13 in stage I, ten in stage II, and six in stage III) and ten were in remission after chemotherapy. Anterior and posterior whole-body scans were obtained 10 min after i.v. injection of 555 MBq of 99mTc-MIBI. The scans were classified as showing: pattern N, when only physiological uptake was present; pattern D, when diffuse bone marrow uptake was observed; pattern F, when areas of focal uptake of the radiotracer were evident; or pattern D+F, when both D and F patterns were observed. Diffuse bone marrow uptake was scored according to extension and intensity. Seven of the 39 patients (18%) showed pattern N, 18 (46%) pattern D, 2 (5%) pattern F, and 12 (31%) pattern D+F. Of the 32 patients with a positive 99mTc-MIBI scan (i.e. showing pattern D, F or D+F), 29 (91%) had active disease. Only three patients in remission showed pattern D, but with a very low bone marrow uptake score. Both extension and intensity of diffuse bone marrow uptake correlated with the amount of the monoclonal component and the percentage of bone marrow plasma cells. The distribution of the 99mTc-MIBI uptake patterns differed among patients in different stages of disease. Using as criteria for advanced stage the presence of either focal uptake (pattern F or D+F) or pattern D with a high score, high (90%) diagnostic accuracy was obtained. In conclusion, the patterns of 99mTc-MIBI uptake in patients with MM are related to both the clinical status and the stage of disease. The presence of focal uptake or of intense diffuse bone marrow uptake suggests that the patient has active and advanced stage disease, while a negative scan in a patient with MM clearly indicates remission.
The RET proto-oncogene product is a receptor tyrosine kinase representing the signal-transducing molecule of a multi-subunit membrane receptor complex for at least two different types of transforming growth factor (TGF)-beta-related neurotrophic factors. We have previously shown that RET gene expression in acute myeloid leukemia (AML) occurs more frequently in AMLs displaying either a monocytic (FAB M4/M5) or intermediate-mature myeloid phenotype (FAB M2/M3) than in leukemias reflecting an earlier stage of myeloid differentiation (FAB M0/M1). To further verify the association between RET expression and the relative maturation stage of AML cells, we have performed a quantitative estimation of relative abundances of RET transcripts among various FAB subtypes of AMLs. By analyzing 13 AML samples and normal hematopoietic cells through a competitive-quantitative RT-PCR approach, we were able to show that the relative levels of RET-specific mRNAs continuously increase with blast cell maturation in human AML, i.e., the amounts of RET gene-specific transcripts differ among RET-expressing AMLs, being higher in the more differentiated FAB phenotypes. In addition, we provide evidence that the relative amounts of RET transcripts increase upon in vitro and in vivo differentiation of leukemic promyelocytes from FAB M3 AML patients, becoming overall comparable to those found in normal granulocytes. These results indicate that RET expression in human AMLs is maturation-associated, probably mirroring the developmental regulation of this gene during differentiation of normal hematopoietic cells.
OBJECTIVES: This study sought to describe the ability of transesophageal echocardiography (TEE) to document the presence of penetrating atherosclerotic aortic ulcers and their complications. BACKGROUND: TEE has greatly enhanced our ability to assess patients with suspected aortic disease. However, the utility of this technique in the diagnosis of penetrating atherosclerotic aortic ulcers is still undefined. METHODS: TEE was performed prospectively in 194 patients to evaluate aortic disease. Twelve patients with the diagnosis of aortic ulcers or their complications were specifically studied. The diagnosis was confirmed by pathologic studies in six patients and by an additional diagnostic technique (angiography, computed tomography or magnetic resonance imaging) in the other six. All 12 patients were hypertensive and presented with chest or back pain; the mean age was 65 years (range 56 to 79). The initial working diagnosis was acute aortic dissection in nine patients. Aortic ulcers were located in the descending thoracic aorta in eight patients, the aortic arch in two and the ascending aorta in two. RESULTS: TEE could detect aortic ulcers or their complications in 10 patients but failed to detect these lesions in the remaining 2 (1 with aortic ulcers in the distal ascending aorta and 1 with aortic ulcers in the aortic arch). In four patients, aortic ulcers were detected as a calcified focal outpouching of the aortic wall and were associated with concomitant aneurysmal dilation of the aorta in two patients and with a small localized intramural hematoma in one. TEE visualized a partially thrombosed pseudoaneurysm complicating an aortic ulcer in the descending thoracic aorta of two patients. Four patients had an aortic ulcer complicated by a "limited aortic dissection" in the descending aorta that could be detected by TEE. Five patients underwent operation, two because of aneurysmal dilation of the aorta and three because of aortic dissection; two patients died of aortic rupture; the remaining five did well (11-month follow-up) without operation. CONCLUSIONS: Aortic ulcers should be included in the differential diagnosis of chest or back pain, especially in elderly hypertensive patients. These ulcers and their complications may be recognized by TEE.
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PURPOSE: To evaluate conventional radiography, US and CT in identifying jejuno-ileal perforation. MATERIAL AND METHODS: We retrospectively reviewed the findings of conventional radiography, US and CT in 13 consecutive patients with surgically proven jejuno-ileal perforation. RESULTS: The site of perforation was the ileum in 10 cases and the jejunum in 3 cases. Free gas was identified in 6 cases (46%) while indirect findings of perforation were found in 7 (54%). The jejunal perforations were diagnosed by indirect findings in all 3 cases. The ileal perforations were diagnosed by direct findings in 6 cases and indirect findings in 4 cases. CONCLUSION: Conventional radiology did not detect free gas in 7 (54%) of the 13 patients examined. In the absence of free gas, radiology showed indirect signs in all 7 patients, the most common being intraperitoneal free fluid in 5 (71%) of them. Jejunal perforations were more rare than ileal perforations and more difficult to identify by radiology. US was not useful for detecting free gas but it was useful for identifying intraperitoneal free fluid and intestinal paresis. Abdominal CT was useful when performed 6 h after the symptoms began.
In the elderly, acute myeloid leukemia (AML) is characterized by a poorer prognosis than in younger patients, due to either host related factors (poor performance status, co-morbid diseases, organ function impairment) or the biology of leukemia itself (high incidence of adverse cytogenetic abnormalities, high frequency of preceding myelodysplastic syndromes, intrinsic resistance to cytotoxic drugs). Current therapeutic results are mostly unsatisfactory and studies reporting high rates of complete remission are probably influenced by selection biases as suggested by the low rate of elderly patients inclusion into cooperative trials. Availability of intensive support including hematopoietic growth factors could stimulate clinicians to manage an increasing number of elderly patients with AML with aggressive programs. However, chemotherapy in the elderly is difficult, costly and usually associated with high morbidity and mortality rate. Therefore, all efforts should be made to identify those subset of elderly patients in whom aggressive treatment may result in a true improvement of disease free and overall survival. The critical analysis of our five years experience, as reported here, seems to suggest that older AML patients displaying unfavourable prognostic factors at diagnosis (i.e., adverse karyotype and high serum LDH levels), but clinically eligible for intensive chemotherapy, do not actually benefit from an aggressive approach. A blind attempt to treat these patients aggressively may be associated with a life threatening toxicity not counterbalanced by an actual survival advantage. We suggest therefore that aggressive treatment should be reserved for elderly AML cases in whom the presence of good prognostic factors at diagnosis predicts that the loss of some patients due to toxicity may be balanced by the achievement of a substantial proportion of long term survivors. Finally, given the biological and clinical heterogeneity of elderly AML patients, a more precise prognostic categorization of these patients would be particularly useful in interpreting future therapeutic results.
The authors present the experience of 63 clinical cases of microsurgical reconstruction of the head and neck. These reconstructions were accomplished by different microvascular free flaps which were selected according to the type, size and location of the defects. Fasciocutaneous, osteofasciocutaneous, adipofascial, myo, myocutaneous, myosseous, jejunum and great omentum flaps were applied. The etiology was traumatic in 10 cases, tumoral in 41 cases, congenital in 7 cases, iatrogenic in 3 cases and infectious in 2 cases. The reconstructed anatomical regions were the scalp in 6 cases, the skull base in 1 case, the orbit in 3 cases, the nose in 1 case, the hemiface in 7 cases, the lips in 1 case, the intraoral cavity in 21 cases, the mandible in 8 cases, the intraoral cavity plus mandible in 11 cases and the cervical esophagus in 1 cases. An analysis was made of surgical times, selection and survival rate of the free flaps and the morphofunctional quality of the reconstructions. Considering the good quality of reconstructions, the amelioration of quality of life and the low morbidity in these patients, microvascular free flaps are considered a first choice technique for head and neck reconstruction when the size and location of the defect prevents the use of local flaps.
Sumatriptan, a selective 5-hydroxy-triptamine (5-HT1) receptor agonist, has been used recently in the treatment of acute migraine. Some in vitro experiments suggested that sumatriptan has vasoactive properties in vascular beds distinct from cerebral circulation. In view of this we investigated the vascular effects of the standard 6 mg subcutaneous (s.c.) dose of sumatriptan, on the surface areas of the head using thermography, a simple and reliable method for detecting temperature changes. The head temperature of 127 patients (double-blind), 102 migraines (52 during headache attack and 50 headache-free) and 25 healthy control subjects were evaluated using thermography in basal condition and 30, 60, 90, and 120 min after s.c. sumatriptan injection of placebo. During the entire observation period systemic blood pressure (SBP), heart rate (HR) and continuous electrocardiogram (ECG) were detected automatically. A significant head temperature decrease was observed after s.c. sumatriptan administration, in both healthy controls and migraine subjects; placebo administration did not show any change of temperature. In migraine patients during headache attack, head temperature reduction corresponded to the relief of headache symptoms. This vasoconstrictor effect detected with thermography is not isolated to cranial circulation but it is also systemic. In fact, we observed a significant increase (p < 0.05) in both systolic and diastolic systemic blood pressure. No significant changes in heart rate and ECG abnormalities were otherwise detected. These findings suggest that sumatriptan is effective in the treatment of migraine attack, but it must be used with caution in migraines with concomitant hypertension.