[Community-acquired pneumonia in an alcoholic patient].
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Biomedical subjects
Publications and source records attributed to M Velasco.
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This is the report of a hydranencephalic child with severe generalized seizures of the Lennox-Gastaut Syndrome (LGS) who lacked the development of the entire cerebral hemispheres and had preserved the brain stem, cerebellum, hypothalamus and a portion of the thalamus as evidenced by radiological and/or physiological studies. Conventional polygraphic sleep studies in these patients showed presence of scalp EEG and other peripheral, somatic and vegetative signs characterizing the wakefulness, quiet sleep and active sleep stages. Absence of the vertex waves and disrupted sleep spindles were the major qualitative EEG abnormalities. In contrast, quantitative abnormalities in duration, latency and number of sleep cycles found in this patient were similar to those found in other children with Idiopathic Lennox-Gastaut Syndrome (ILGS). A substantial reduction in the number of interictal EEG spikes and a shortening of the ictal clonic EEG activities without concomitant EMG jerks were the most distinct epileptiform abnormalities in this child. In contrast, his basic polygraphic patterns of the tonic and apneic seizures were similar to those found in other children with ILGS. Data obtained from this child suggest that both the sleep stages and the generalized seizures of the ILGS basically depend more on the integrity of the brain stem than on the telencephalic structures.
We have reviewed the cardiovascular actions of calcioantagonists. These drugs act through L and T channels, inhibiting calcium ions entry at the alpha 1 subunit. The union sites for dihydropiridines (DHPs) are surfacely located (N site) compared to those of diltiazem and verapamil (D and V sites). The administration of calcioantagonists induces peripheral vasodilation with decrease of blood pressure and peripheral resistance; they also act on myocardium inhibiting AV conduction and cardiac contractility. DHPs act more specifically on vascular smooth muscle than myocardium; however, no DHPs (diltiazem and verapamil) act more specifically on myocardium than peripheral vessels. Among drugs of first generation we can mention: nifedipine, diltiazem and verapamil. Among drugs of second generation we have: lacidipine and amlodipine with better tissue selectivity and longer biological half-lives. A recently introduced compound, mibefradil, acts selectively on T channels. The use of calcioantagonists is wide: coronary disease, hypertension, cardiac arrhythmias, ischemic cerebrovascular disease, cardiac failure, primary pulmonary hypertension. World Health Organization has recommended calcium antagonists as first line drugs in hypertension as done with other compounds: diuretics, betablockers, and converting enzyme inhibitors. Recent controversial studies on calcioantogonists should be assessed adequately in order to take a definitive decision.
BACKGROUND: Multiple infective complications have been described in injection drug users (IDUs). Infective endocarditis, most frequently caused by Gram positive bacteria, with classical features, is one of the most dangerous. In a few patients fungi are the cause (less than 5%), and these develop an unusual clinical picture. METHODS: An IDUs patient was admitted in our Hospital for subacute arterial ischemia at the inferior limbs. A mass inside the abdominal aorta was detected by echography and arteriography, which was removed surgically a few hours later. RESULTS: The pathologic evaluation of the surgical specimen revealed its fungal composition; the culture of this material was characteristic of Candida albicans. The clinical suspicion of aortic endocarditis, as the emboligenic source responsible of the inferior limbs ischemia, was confirmed with the performance of an echocardiography. A few hours after surgery the patient got worse; 24 hours later he died due to uncontrolled bleeding of the surgical suture in the aorta. CONCLUSIONS: Fungal endocarditis should be thought in IDUs patients presenting inferior limbs ischemia. Due to the high mortality of this disease, as soon as the diagnosis is suspected, urgent medical and surgical therapy should be started.
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Stimulation of the murine macrophage RAW 264.7 cell line with phorbol esters fails to promote nitric oxide synthesis as occurs in rat hepatocytes or peritoneal macrophages. Transfection of RAW 264.7 cells with plasmids harboring protein kinase C (PKC) -epsilon isotype but not with PKC-alpha, -beta1, -delta, or constitutively active -alpha and -beta1 isotypes resulted in the expression of nitric oxide synthase type II (iNOS), as reflected by the synthesis of nitric oxide measured in the culture medium of transfected cells. cotransfection of RAW 264.7 cells with the -1592 to +121-base pair promoter region of the murine iNOS gene and PKC isotypes specifically induced the transactivation of this promoter in the case of the plasmids containing the PKC-epsilon isotype. The mechanism by which PKC-epsilon induced iNOS expression involved the activation of nuclear factor binding to kappaB sites (NF-kappaB) as deduced by the suppressive effect of pyrrolidine dithiocarbamate on nitric oxide synthesis, an inhibitor of NF-kappaB activation, and by the activation of kappaB sites in cells transfected with a vector containing a kappaB motif linked to a chloramphenicol acetyltransferase reporter gene. These results suggest that PKC-epsilon can regulate a pathway that promotes iNOS expression in macrophages in response to phorbol ester activation.
Incubation of primary cultures of rat hepatocytes with lipopolysaccharide (LPS), S-[2,3-bis(palmitoyloxy)-(2-R, S)-propyl]-N-palmitoyl-(R)-Cys-Ser-Lys4 (TPP), a synthetic lipopeptide present in bacterial cell wall lipoproteins, or with phorbol 12,13-dibutyrate (PDBu) induced an increase in nitric oxide synthesis through the expression of type II nitric oxide synthase (iNOS). Transfection of hepatocytes with a HindII fragment corresponding to the promoter region of the murine iNOS gene (from nucleotide -1588 to +165) resulted in the expression of the reporter gene when cells were stimulated with these factors. The transcription factors activated by these stimuli involved an increase in the nuclear content of proteins that bind to kappaB, AP-1, GAS, and SIE sequences. Inhibition of NF-kappaB activation with pyrrolidine dithiocarbamate eliminated the expression of iNOS in hepatocytes stimulated with LPS, TPP, or PDBu. In addition to this, transfection of hepatocytes with promoter mutants in which a sequential 2-base pair change within the kappaB sites was introduced (position -971 to -961 and -85 to -75, respectively), resulted in approximately 17 and 35%, respectively, of the activity of the naive promoter. Simultaneous mutation of both kappaB sites abolished the promoter activity. Analysis of the proteins involved in kappaB binding showed the presence of p50/p65 dimers in the nuclei of activated cells at the time that an important decrease of IkappaB-alpha was observed soon after cell stimulation with LPS, TPP, or PDBu. However, only LPS was able to decrease the amount of IkappaB-beta. These results suggest that LPS, TPP, and PDBu, although activating different signal transduction pathways, use a common mechanism mediating iNOS expression in cultured hepatocytes.
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To evaluate the utility of c-erbB-2, carcinoembryonic antigen (CEA) and CA 15.3 in the early diagnosis of recurrence, serial serum determinations of these antigens were performed in 200 patients (follow-up 1-4 years, mean 2.2 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Eighty-nine patients developed metastases during follow-up. C-erbB-2, CEA and CA 15.3 were elevated (> 20 U ml-1, > 10 ng ml-1 or > 60 U ml-1 respectively) before diagnosis in 28%, 30% and 47% of the 89 patients with recurrence, with a lead time of 4.5 +/- 2.4, 4.9 +/- 2.4 and 4.8 +/- 2.4 months respectively. Tumour marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver metastases. When patients with locoregional recurrences were excluded, sensitivity improved: 31% (c-erbB-2), 33% (CEA) and 56% (CA 15.3), with 76% having at least one of the three tumour markers. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (8/10, 80%) than in those without overexpression (1/30, 3.3%) (P = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PR+ patients (CA 15.3, P < 0.0001) or in PR- patients (c-erbB-2, P = 0.009). Specificity of the tumour markers was 100% for all three markers (111 NED patients). In conclusion, c-erbB-2 is a useful tool for early diagnosis of metastases, mainly in those patients with c-erbB-2 overexpression in tissue. Using all three markers simultaneously it is possible to increase the sensitivity in the early diagnosis of recurrence by 11.2%.
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Malignant endovascular papillary angioendothelioma, first described by Dabska in 1969, is a rare vascular tumor that primarily affects children and is characterized by papillary proliferations of endothelial cells into vessel lumens. We report a case of this rare neoplasm in a boy with angiomatosis who developed Kasabach-Merritt syndrome. The tumor evolved as an ulcerated lesion superficially within a previous vascular malformation on his buttock. A review of the literature is presented.
The use of peripheral blood as a source of hematopoietic precursors is an alternative to the bone marrow in allogeneic transplantation. Although pediatric allogeneic PBPC experience is limited, there is no reason to believe that the outcome and benefit with PBPC should be different than adults. We describe our initial experience in two children who received PBPC allogeneic transplantation in whom the donors were mobilized with filgrastim. Hematopoietic recovery was achieved on days 14 and 16, and the patients did not develop severe GVHD.
In the present study we evaluated the effect of intravenous metoclopramide on blood pressure in normotensive (untrained, football players, runners) and hypertensive subjects. There was a decrease in blood pressure only observed in untrained female subjects and this was greater in hypertensive subjects. In football players and runners the decrease in blood pressure was not statistically significant. There was no significant effect on heart rate. The probable mechanism of this new pharmacological effect of metoclopramide is unknown, however, research is now in progress to define its mechanism of action.
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A modern approach to the choice of antihypertensive therapy is discussed in this article. Since the introduction of hydralazine and reserpine in 1950, a number of compounds have been proposed for the treatment of hypertension. The 1993 report of the Joint National Committee on Hypertension established four choices: diuretics, beta blockers, ACEIs, and calcium entry blockers. Additionally, alpha and alpha-beta blockers were also recommended. Several pharmacological considerations have been discussed concerning medical therapy of hypertension. In modern therapy, the best approach is individualized therapy, in which three major principles are taken into consideration: (1) The use of diuretics, alpha blockers, beta blockers, ACEIs, or calcium entry blockers, (2) The presence of concomitant diseases, and (3) The use of substitution therapy. Several other factors are discussed such as the cost of medication, drug interactions and combinational therapy.
Leukemic relapse after allogeneic bone marrow transplantation or allogeneic peripheral blood progenitor cell transplantation arises normally from residual malignant host hematopoiesis. The lack of specific tumor markers in acute lymphoblastic leukemia presents a problem for detection of residual disease post-infusion. In the present prospective study, we used PCR amplification of variable numbers of tandem repeat genetic regions for close follow-up of chimeric status in order to try to distinguish those patients at high risk of relapse. We found that chimeric status evolution was different between the long-term surviving patients and relapsed patients. The former showed either donor chimerism (DC) or transient mixed chimerism (tMC), while the latter always showed a recipient-growing MC (r.gMC). In addition, we found that complete substitution of hematopoiesis was achieved better with radiation-containing regimens, and that chronic graft-versus-host disease never appeared in MC patients. We conclude that very close follow-up of serial samples can facilitate the early detection of those leukemic children with a poor outcome after hematopoietic cell transplantation.
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