Trombólise em paciente jovem com tromboembolia pulmonar aguda de risco intermediário alto bem sucedida / Thrombolysis in a young patient with acute intermediate high-risk acute pulmonary embolism

INTRODUÇÃO: O Tromboembolismo pulmonar (TEP) agudo é uma condição bastante prevalente e potencialmente fatal, é a terceira maior causa de mortalidade cardiovascular mundial, sendo crucial suspeita e condução adequadas. Após diagnóstico do TEP agudo, deve-se avaliar sua repercussão clínica, sendo considerado de alto risco aquele com instabilidade hemodinâmica, devendo ser tratado com trombolítico para reperfusão. Esta conduta, nos casos de risco intermediário é controversa. Relato: Relato de caso de paciente sexo feminino, 33 anos, obesa e portadora de sd ovário policístico, que procurou pronto socorro (PS)por dispnéia progressiva e dor torácica opressiva há 10 dias. Diagnosticada com TEP após Angiotomografia Tórax e estratificada como risco intermediário alto. Paciente apresentava AngioCT Tórax com falha de enchimento importante em bifurcação das arterias pulmonares (oclusão > 50% luz). Observado em ECO TT da admissão (urgência) aumento moderado câmaras cardíacas direitas, hipocontratilidade de segmento basal e parede livre de VD, com presença hipercontratilidade em ápice de VD (sinal McCONNEL). Dosagem NT pro-BNP 2740,00 (Valor Normalidade < 125). Paciente apresentava-se sintomática porém mantendo estabilidade hemodinâmica. Fora então optado por terapia trombólise com alteplase 100mg em 02 horas. Houve resposta e evolução satisfatória. Em ECO TT (após 10 dias) houve melhora função sistolica VD e de Hipertensão Pulmonar em comparação ao exame prévio. Recebeu alta em uso de Anticoagulante Oral varfarina, com dispneia Classe Funcional II. Feito contato telefônico com paciente após 10 meses, referindo dispneia CF I, sem limitação para atividades diárias. CONCLUSÃO: O tratamento do TEP risco intermediário alto é controverso em protocolos mundiais; A conduta apresentada com trombólise foi de suma importância para o desfecho apresentado, evitando que uma paciente jovem evoluísse para insuficiência cardíaca com interferência importante em sua qualidade de vida.

Lack of significant estrogenic or antiestrogenic activity of pyrethroid insecticides in three in vitro assays based on classic estrogen receptor alpha-mediated mechanisms.

Estrogenic and antiestrogenic activity of pyrethroid insecticides (d-trans-allethrin, cypermethrin, empenthrin, fenvalerate, imiprothrin, permethrin, d-phenothrin and prallethrin) was evaluated using a suite of three in vitro assays based on classic human estrogen receptor alpha (hER alpha)-mediated mechanisms. A mammalian cell-based luciferase reporter gene assay was developed for examining effects on hER alpha-mediated gene activation. hER alpha-independent effects on the gene activation were examined using control cells with constitutive luciferase activation by a herpes simplex virus thymidine kinase (HSV-TK) promoter for determining appropriate dose levels of test chemicals. Moreover, the test chemical-dependent interaction between hER alpha and a coactivator (transcriptional intermediary factor 2: TIF2) was analyzed by a yeast two-hybrid method, competitive binding to hER alpha being assayed by a fluorescence polarization method. Significant (p < 0.05) positive effects of estrogenic substances (E2/estradiol, diethylstilbestrol, and p-nonylphenol) were detected in all assays. An antiestrogen, 4-hydroxytamoxifen, significantly inhibited E2-mediated transactivation and interaction between hER alpha and TIF2 through hER alpha binding (p < 0.05). However, none of the pyrethroids tested showed significant (p < 0.05) estrogenic or antiestrogenic effects (100 nM-10 microM), indicating that they do not impact on the classic hER alpha-mediated activation pathway in vitro.

Secondary tethered cord syndrome in spinal dysraphism.

Secondary tethered cord syndrome following initial repair for spinal dysraphism is an important area of interest. In this study, 32 cases with spinal dysraphism in the lumbosacral region were enrolled, in whom radical repair with autologous material had been carried out in the early stage soon after birth. During the follow-up period of up to 19 years 10 months, surgery was considered to be indicated in 2 of the 8 lipomeningocele cases and in 6 of the 24 meningocele and meningomyelocele cases, because of the presence of tethered cord syndrome 4-19 years after the primary operation. In all 8 of these cases, MR imaging demonstrated tethered spinal cord in the form of low conus medullaris. In 6 of the 8 operated cases surgery was followed by improvement of the spinal neurological deterioration. According to our experience, early untethering for secondary tethered cord syndrome is essential. In addition, since the complications of Silastic duraplasty at untethering were all minor and the operative outcome was satisfactory, the use of silicone rubber sheeting as a dural substitute might be recommended to prevent adhesion of the spinal cord.

A case in which stent insertion is considered to have triggered contrast medium-induced coronary vasospasm.

A Gianturco-Roubin II (GR-II) stent was inserted in a 75-year-old man who developed restenosis of the right coronary artery (RCA) after percutaneous transluminal coronary angioplasty (PTCA). Although the vessel became partially occluded after 7 months, it was redilated by PTCA. Follow-up angiography of the RCA and left coronary artery (LCA) was performed 3 months later. Chest pain with bradycardia and hypotension occurred immediately after this examination, and ST elevation appeared in ECG leads II, III, and aVF. Repeat angiography of the RCA confirmed complete occlusion due to a spasm at a site proximal to the GR-II stent. The spasm was resolved by intracoronary infusion of isosorbide dinitrate (ISDN), and PTCA was carried out for extensive recurrent restenosis of the RCA; however, vascular dissection developed at the distal end of the GR-II stent. Therefore, a Palmaz-Schatz (P-S) stent was placed such that its proximal end overlapped the distal end of the GR-II stent. Follow-up angiography 3 months later showed no restenosis, but an episode of vasospasm similar to the previous one occurred immediately after left ventriculography. The RCA was completely occluded proximal to the GR-II stent because of spasm. Although this spasm was gradually relieved by intracoronary infusion of ISDN, marked spasm was also observed distal to the P-S stent; complete relief was achieved by infusion of additional ISDN.

Significance of acute cerebral swelling in patients with sylvian hematoma due to ruptured middle cerebral artery aneurysm, and its management.

A retrospective study of 75 patients treated surgically for ruptured middle cerebral artery (MCA) aneurysm within 48 hours evaluated clinical grade at admission, secondary development and management of cerebral swelling associated with space-occupying hematoma, cerebral infarction caused by vasospasm, development of hydrocephalus, and clinical outcome. Clinical grade at admission was significantly better in patients without than in those with hematoma (p < 0.01). Twenty-seven patients with sylvian hematoma caused by ruptured MCA aneurysm often developed ipsilateral cerebral swelling in the early period after subarachnoid hemorrhage. Seventeen of these patients developed serious cerebral swelling and received barbiturate therapy. Nine of these 17 patients had good outcome, but six patients died of cerebral swelling. The incidence of hydrocephalus was significantly higher in patients with than in those without hematoma (p < 0.01). The incidence of infarction was more pronounced in patients with sylvian hematoma. Clinical outcome was significantly better in patients without than in those with sylvian hematoma (p < 0.01). Development of cerebral swelling in patients with sylvian hematoma due to ruptured MCA aneurysm has a significant effect on outcome, and improvements in management are required.

Modulation of cell-adhesive activity of fibronectin by the alternatively spliced EDA segment.

Fibronectin (FN) has a complex pattern of alternative splicing at the mRNA level. One of the alternatively spliced segments, EDA, is prominently expressed during biological processes involving substantial cell migration and proliferation, such as embryonic development, malignant transformation, and wound healing. To examine the function of the EDA segment, we overexpressed recombinant FN isoforms with or without EDA in CHO cells and compared their cell-adhesive activities using purified proteins. EDA+ FN was significantly more potent than EDA- FN in promoting cell spreading and cell migration, irrespective of the presence or absence of a second alternatively spliced segment, EDB. The cell spreading activity of EDA+ FN was not affected by antibodies recognizing the EDA segment but was abolished by antibodies against integrin alpha5 and beta1 subunits and by Gly-Arg-Gly-Asp-Ser-Pro peptide, indicating that the EDA segment enhanced the cell-adhesive activity of FN by potentiating the interaction of FN with integrin alpha5beta1. In support of this conclusion, purified integrin alpha5beta1 bound more avidly to EDA+ FN than to EDA- FN. Augmentation of integrin binding by the EDA segment was, however, observed only in the context of the intact FN molecule, since the difference in integrin-binding activity between EDA+ FN and EDA- FN was abolished after limited proteolysis with thermolysin. Consistent with this observation, binding of integrin alpha5beta1 to a recombinant FN fragment, consisting of the central cell-binding domain and the adjacent heparin-binding domain Hep2, was not affected by insertion of the EDA segment. Since the insertion of an extra type III module such as EDA into an array of repeated type III modules is expected to rotate the polypeptide up to 180 degrees at the position of the insertion, the conformation of the FN molecule may be globally altered upon insertion of the EDA segment, resulting in an increased exposure of the RGD motif in III10 module and/or local unfolding of the module. Our results suggest that alternative splicing at the EDA exon is a novel mechanism for up-regulating integrin-binding affinity of FN operating when enhanced migration and proliferation of cells are required.

Correlation between blood parameters and symptomatic vasospasm in subarachnoid hemorrhage patients.

Serial changes in platelet and white blood cell (WBC) counts and other blood parameters were analyzed in 103 patients with aneurysmal subarachnoid hemorrhage (SAH). The WBC counts during days 3-5, 6-8, 9-11, and 12-14 after the onset of SAH were significantly higher in patients with than in patients without symptomatic vasospasm. Platelet counts during days 0-2, 3-5, 6-8, 9-11, 12-14, 15-17, 18-21, and 22-28 after SAH were significantly higher in patients with than in patients without symptomatic vasospasm. Monitoring of platelet and WBC counts may provide an indicator of the occurrence of symptomatic vasospasm.

Cardiopulmonary effects of sevoflurane in cats: comparison with isoflurane, halothane, and enflurane.

The cardiopulmonary effects of sevoflurane (mean, 2.6, 3.8-3.9 and 5.2 per cent) were compared with those of halothane (1.2, 1.8 and 2.4 per cent), enflurane (2.4, 3.6 and 4.8 per cent) and isoflurane (1.6, 2.4 and 3.2-3.3 per cent) at end-tidal concentrations equivalent to 1, 1.5 and 2 minimal alveolar concentrations (MACs) during spontaneous or controlled ventilation (SV or CV) in 57 cats. Cats were assigned to four groups of nine animals each in SV trial and four groups of five or six animals each in CV trial. During SV, respiration rate was decreased by sevoflurane and isoflurane at 2 MAC and by enflurane at each MAC multiple when compared with control values, whereas halothane increased respiration rate at 2 MAC. The degree of hypercapnia and acidosis induced by sevoflurane was not different from that induced by isoflurane and was less than that induced by halothane at 1 to 1.5 MAC or enflurane at 2 MAC. During SV and CV, four anaesthetics decreased heart rate at 2 MAC when compared with control values, but there was no significant difference between anaesthetics. Sevoflurane, like halothane and isoflurane, induced hypotension at 2 MAC when compared with 1 MAC.

How can the bioavailability of timolol be enhanced? A pharmacokinetic pilot study of novel hydrogels.

BACKGROUND: Carbomerbased hydrogels with timolol maleate (T-Gel) were chosen to study the vehicle effect on ocular bioavailability. Pharmacokinetic profiles of T-Gel 0.05% (0.05% timolol), T-Gel 0.025% (0.025% timolol) and commercial timolol ophthalmic solution (TOS 0.1%; 0.1% timolol) were determined and compared. METHODS: A single dose was administered to rabbits' eyes. Timolol was determined by HPLC in aqueous humour, blood samples and washings of the ocular surface (as a measure of residence time). Sampling times were 0.5 h, 1 h and 4 h after instillation. RESULTS: Concentration versus time curves (AUC) of timolol in aqueous humour demonstrate no significant differences between TOS 0.1% and T-Gel 0.025% (P = 0.19), whereas the difference between T-Gel 0.05% and TOS 0.1% is significant (P = 0.006); the AUC ratio of T-Gel 0.05%:TOS 0.1%:T-Gel 0.025% was 2.14:1:0.87. Timolol blood levels were highest with TOS 0.1% at every time point. Peak levels occurred after 0.5 h with all test products; the ratio of peak levels (Cmax) for T-Gel 0.05%:TOS 0.1%:T-Gel 0.025% was 0.55:1:0.17. Timolol was detected in the washings up to 1 h after instillation of test products; the highest levels were observed after T-Gel 0.05%. CONCLUSION: The new vehicle obviously improves the bioavailability of topically applied timolol.

Efficacy of a novel hydrogel formulation in human volunteers.

In a two-period crossover study, 20 subjects without an ocular disease received single doses of either a novel timolol hydrogel (T-Gel 0.1%) or aqueous timolol 0.5% in one eye and placebo in the fellow eye. Diurnal variation curves of intraocular pressure of both eyes were obtained for a 24-hour period. Peak effects up to -30% of the baseline were observed. A statistically significant residual effect was still detectable 24 h after application. The timolol gel had the same efficacy in lowering intraocular pressure as the commercially available aqueous timolol solution with a five times higher strength. Equivalence of treatment effects was statistically proved.

Possible function of Ah receptor nuclear translocator (Arnt) homodimer in transcriptional regulation.

Arnt (Ah receptor nuclear translocator) is a member of a transcription factor family having characteristic motifs designated bHLH (basic helix-loop-helix) and PAS and was originally found as a factor forming a complex with Ah receptor (AhR) to bind the specific xenobiotic responsive element (XRE) sequence for induction of drug-metabolizing P4501A1. We have examined interaction of Arnt with other PAS proteins--Drosophila Per, Sim, and AhR--by the coimmunoprecipitation method. Arnt formed a homodimer with itself as well as heterodimers with the others by means of the PAS and HLH domains in a cooperative way. The Arnt homodimer binds the sequence of adenovirus major late promoter (MLP) with the E box core sequence CACGTG, suggesting that the CAC half of the XRE, CACGCN(A/T), recognized by the AhR-Arnt heterodimer is a target for Arnt. Cotransfection experiments using CV-1 cells with an Arnt expression plasmid and a MLP chloramphenicol acetyltransferase (CAT) reporter plasmid revealed that Arnt markedly activated CAT expression, indicative of a newly discovered regulatory role of Arnt.

Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese--class II antigen and autoimmune thyroid disease.

HLA-DQA1 and DPB1 alleles were examined in relation to autoimmune thyroid disease (AITD) in the Japanese type 1 diabetic patients. The subjects consisted of 14 type 1 diabetic patients with Graves' disease, 12 patients with Hashimoto's thyroiditis and 32 type 1 diabetic patients without AITD. Comparisons were made with 35 normal controls. Among the type 1 diabetic patients with Graves' disease, the age at onset of diabetes was 31.8 +/- 14.6 years old, which was later than that of those without AITD (P < 0.01). DR9 was increased (57.1% vs. 25.9%, P < 0.05, RR: 3.85, chi 2:4.36) in the patients with Graves' disease. DQA1*0301 was increased and DQA1*0103 was decreased in the patients with Graves' disease and those without AITD. HLA-DPB1*0501 was increased (92.9% vs. 54.3%, P < 0.05, RR: 11.0, chi 2:6.57) in the patients with Graves' disease. These findings suggest the existence of a Graves' complicated subgroup characterized by the increasing association of DPB1*0501 and late onset of diabetes in Japanese type 1 diabetic patients. There exists a heterogeneity in Japanese type 1 diabetes.

Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors.

The genetic difference in the susceptibility of mice to environmental toxicities induced by dioxin and related chemicals is governed by polymorphism of the arylhydrocarbon receptor (AhR) (Poland, A., and Knutson, C. (1982) Annu. Rev. Pharmacol. Toxicol. 22, 517-554). cDNA cloning of AhR cDNA from responder (C57BL/6) and non-responder (DBA/2J) mice allowed us to analyze the structure and function of these AhRs. Both of the AhRs, which were expressed in COS-7 cells transfected with their expression plasmids, showed a clear 9 S complex with 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin (TCDD) in a linear glycerol gradient centrifugation, consistent with the result of the endogenously expressed AhR in Hepa-1 cells. This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. Scatchard plot analysis revealed that the dissociation constant (Kd) of C57BL AhR for TCDD is 0.27 nM, while that of DBA AhR is elevated up to six times that high. Chimeric plasmids between the two cDNAs and site-directed mutagenesis revealed two critical alterations responsible for the reduced ligand binding activity: an Ala375 to Val alteration and an elongated carboxyl-terminal sequence due to a T to C mutation at the first letter of the termination codon of C57BL AhR. Two variants with reduced and intermediate ligand binding activity were also found in human AhRs with amino acid alterations equivalent to those of the DBA AhR. Importance of the amino acid at position 381 of human AhR (equivalent to position 375 of mouse AhR) in the ligand binding was confirmed by the fact that the mutation of Val381 to Asp completely abolished the ligand binding activity of human AhR.

[Vertebral artery injury following mild neck trauma: report of two cases].

Two cases of vertebral artery injury following mild neck trauma are reported. A 52-year-old man was hospitalized with gait disturbance 7 days after mild traffic accident. Right vertebral angiogram revealed complete occlusion of the rt. vertebral artery (VA) and MR images revealed infarction in the rt. cerebellar hemisphere and rt. dorsolateral part of the medulla oblongata and revealed the thrombus in the rt. VA. He underwent anticoagulation and became asymptomatic. Angiogram 6 months later revealed the vessel to be normal. A 23-year-old man who has a habit of self-manipulation of his neck was hospitalized on the day when he experienced dysesthesia in the left part of his face and left upper and lower extremities and unsteady gait. MR images revealed multiple infarction in bilateral cerebellar hemispheres and thrombus in bilateral VAs. Bilateral vertebral angiogram revealed severe stenoses of bilateral VAs. He underwent anticoagulation and wore soft collar. Angiogram 20 days after onset revealed improvement of bilateral VA stenoses. He was discharged with no neurological deficit. It is said that vertebral artery injuries in association with head and neck trauma are relatively rare, but this condition is possible to be more common than realized, considering that the case of unilateral VA occlusion or the case with well developed collateral circulation is sometimes well tolerated for ischemia and that this condition can occur even after mild head and neck injury. The diagnosis must be established by vertebral angiogram, but MRI and MRA are very useful as ancillary methods. The therapeutic point is to prevent propagation of the thrombus and distal embolism, accordingly wearing a collar and anticoagulation are important.

Chromosomal localization and cDNA sequence of human BTEB, a GC box binding protein.

Human BTEB cDNA clones have been isolated, sequenced, and the corresponding gene has been assigned to human chromosome 9, region q13, by fluorescent in situ hybridization and DNA blot analysis using DNAs from hybrid cell clones containing a single human chromosome. The cDNA clone encodes a polypeptide of 244 amino acids whose sequence shows a high sequence similarity with the rat BTEB (98% amino acid identity).

[Study of 123I-IMP SPECT on diabetic patients].

The involvement of peripheral nerves and nerve roots often leads to neurological manifestations which have frequently been described in association with diabetes mellitus. Whether there is any specific involvement of the central nervous system in this process has yet to be determined. Recently, many reports have suggested that significant neurophysiologic abnormalities in the central nervous system can sometimes be found in diabetic patients. In order to accurately examine the existence of central nervous system involvement in patients with diabetes mellitus, comparisons of 123I-IMP (IMP) washout rates were made between normal adults (n = 19, average age 43.3 years) and diabetic patients (n = 23, average age 43.3 years), and these results were graphically demonstrated by color images. Early images were obtained 30 minutes after intravenous injection, while delayed images were made 4 hours after injection. The IMP washout rate was obtained by subtracting the values of the delayed image with the early image. The standard deviation (SD) of the IMP washout rate for each patient was compared to the averaged SD obtained from healthy adults. After calculating the deviation from SD levels of healthy adults, we made an image of the patient's IMP washout rates. These images were divided into seven degrees (I, II: normal, III, IV: borderline, V-VII: abnormal) and the ratio of each degree was expressed by a histogram in each cerebral hemisphere as the washout rate index. In 23 diabetic subjects, seven patients were found to be borderline while sixteen patients were abnormal. These impairments were not related either to the presence of diabetic neuropathies or the duration of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[Brainstem ptosis (midbrain ptosis) associated with mesencephalic hemorrhage].

We reported a patient with a brainstem ptosis (midbrain ptosis) associated with mesencephalic hemorrhage. A 57-year-old woman had the sudden onset of bilateral blepharoptosis and diplopia. On admission, computed tomography of the brain and magnetic resonance imaging disclosed a small hematoma in the left tegmentum of midbrain. She had no past history of hypertension of head trauma. Cerebral angiography gave no additional informations. The lesion involving the central caudal subnucleus of IIIrd nerve nucleus may be responsible for the bilateral ptosis, since this finding is consistent with current models of oculomotor organization in monkeys (Warwick 1953).

CT demonstration of spinal epidural emphysema after strenuous exercise.

We report a case of spinal epidural emphysema after strenuous exercise. The emphysema was without clinical signs and disappeared after 2 weeks.