Current and Practical Management of Acute Myocardial Infarction

Journal of Thrombosis and Thrombolysis -     

Long-term follow-up of antimitochondrial antibody-positive autoimmune hepatitis

Antimitochondrial antibodies (AMAs) are the serological hallmark for primary biliary cirrhosis (PBC). When AMAs are detected in patients with chronic hepatitis, they negatively impact on the autoimmune hepatitis (AIH) scoring system. The purpose of this study was to determine if AMAs detected in the sera of patients with overt AIH have clinical or pathological significance. All patients with a clinicopathologic diagnosis of AIH from one center were reviewed. Only those meeting the criteria for probable or definite AIH according to the International Autoimmune Hepatitis Group were included. Patients found to be consistently AMA-positive via enzyme-linked immunosorbent assay (ELISA) for pyruvate dehydrogenase complex E2 subunit were reviewed in detail. Fifteen of 126 patients with typical features of AIH (pretreatment AIH score >10) had detectable AMAs in serum. None had any histologic features suggestive of PBC. None had detectable anti-liver-kidney-microsomal antibodies. Of these 15 patients, all have remained persistently AMA-positive via ELISA. All 15 patients have been followed long-term, and their clinical course remained typical for AIH. No bile duct damage typical of PBC was seen on initial or follow-up liver biopsies. CONCLUSION: Patients with overt AIH who test positive for AMAs at initial presentation and are treated with corticosteroid therapy have shown no clinical or histologic evidence of PBC despite the continued detection of AMAs over a follow-up of up to 27 years.     

Tra2beta as a novel mediator of vascular smooth muscle diversification

Transformer splicing regulatory proteins determine the sexually dimorphic traits of Drosophila. The role of the vertebrate homologs of Tra-2 in phenotypic specification is undefined. We are using the alternative splicing of the MYPT1 E23 exon as a model for the study of smooth muscle diversification into fast and slow contractile phenotypes. Tra2beta mRNA and protein is expressed at up to 10-fold higher levels in fast smooth muscle tissues such as the rat portal vein and small mesenteric artery, in which E23 is spliced, as compared to the slow smooth muscle tissues of the large arteries and veins, in which E23 is skipped. Tra2beta is upregulated up to 10-fold concordant with the initiation of E23 splicing as the rat portal vein and avian gizzard implement the fast program of gene expression in the perinatal period. In disease models such as portal hypertension and mesenteric artery high/low flow, the portal vein and first order mesenteric artery dynamically downregulate Tra2beta concordant with a shift to E23 skipping and the slow program of gene expression. Tra2beta binds to a highly conserved sequence within E23 and transactivates its splicing in vitro and in vivo; this is abolished with mutation or deletion of this sequence. RNA interference-mediated knockdown of Tra2beta markedly reduces E23 splicing. We propose that Tra2beta has been conserved through evolution and redeployed for the specification of the fast smooth muscle phenotype and may serve as a novel nodal point for the investigation of this process in developmental and disease models.     

Foreign body inhalation in children: Decisive factors for carrying out bronchoscopy

Inhalation of Foreign Body is one of the most common causes of accidental death at home in the paediatric age group. There may not be a clear history of foreign body inhalation and the patient may be asymptomatic at initial presentation. This coupled with the failure of radiological investigations on most occasions makes this a vexing clinical situation. These apparently normal children almost invariably have a bad prognosis if the foreign body is ignored. This study aims to define the most important factors influencing the decision to carry out the definitive surgery, i.e., bronchoscopy, which can be diagnostic as well as therapeutic, based on our experience with 50 cases of suspected FB in the tracheobronchial tree from January 2001 to July 2003. Results from the study suggest that radiological investigations have only limited value in deciding the management of a patient with suspected Foreign Body inhalation. This should not influence the decision to carry out a bronchoscopy, which should rather be based on history and clinical examination.     

An analysis of the UNOS liver transplant registry: high serum alpha-fetoprotein does not justify an increase in MELD points for suspected hepatocellular carcinoma.

The current United Network for Organ Sharing (UNOS) criteria for liver transplantation gives priority to patients with elevated serum alpha-fetoprotein (AFP; > or = 500 ng/mL) in the absence of radiologic evidence of a hepatic mass. Reports have shown that an elevated serum AFP is a poor diagnostic indicator for hepatocellular carcinoma (HCC) in patients with cirrhosis. Our aim was to determine if an AFP level above 500 ng/mL, in the absence of a liver mass by imaging study, correlates with the presence of HCC. Using the UNOS database we identified all patients transplanted for HCC in the United States between February 2002 and October 2005 based on these criteria. The data collected included: patient demographics, clinical information, and pathological outcomes. The data was analyzed using a chi-squared t-test and confirmed by logistic regression modeling. A total of 22 patients received a cadaveric liver transplant, while 1 received a living donor transplant during the study period. HCC was confirmed posttransplantation in only 6 patients (26%). There was no difference in race, gender, etiology of liver disease, or AFP level between patients with and without HCC but a significant difference in age (59.8 yr for HCC patients vs. 51.3 yr for the non-HCC group; P = 0.01). In conclusion, the majority of the patients who received extra Model for End-Stage Liver Disease (MELD) points based on an elevated AFP did not have HCC. Older age was a significant predictor for the presence of HCC in patients with a serum AFP greater than 500 ng/mL. These results demonstrate the poor correlation of serum AFP with the presence of HCC in patients awaiting liver transplantation.     

Papulonecrotic Tuberculid

Eleven cases of papulonecrotic tuberculid (PNT) were seen at the Institute of Dermatology, Bangkok, over a 2-year period (1985 to 1986). The diagnosis was supported clinically by symmetric, scattered, papulopustular necrotic lesions, healed with atrophic scars; strongly positive tuberculin test; histopathologic findings; and a rapid improvement after antituberculous therapy. Despite multiple-drug therapy, three cases had recurrences after discontinuation of treatment. Long-term treatment is recommended for the treatment of PNT.     

Action of Δ9-tetrahydrocannabinol on membrane-bound monoamine oxidase activity

In vivo administration (ip) of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) to adult rats under acute conditions (10 and 50 mg/kg) produced a dose-dependent stimulation of monoamine oxidase (MAO; monoamine: O₂ oxidoreductase (deaminating), EC 1.4.3.4) activity in blood platelets and in mitochondrial preparations of hypothalamus and heart. Chronic treatment (10 mg/kg/day for 15 consecutive days) produced a smaller stimulating effect on MAO activity of these tissues. In vitro treatment with Δ⁹-THC produced (1) a stimulatory effect in hypothalamic MAO up to a concentration of 4 μg/mg of protein, (2) an inhibitory effect on heart MAO, and (3) a slight though not insignificant inhibitory effect on platelet MAO. Kinetic studies of in vivo and in vitroΔ⁹-THC-treated enzyme (MAO) are discussed on the basis of K_m and V_max values obtained from Linewwaver-Burk plots. When KSCN, KNO₃, and urea were used, they produced a significant inhibitory effect on MAO activity in all these tissues, even in the presence of Δ⁹-THC, indicating that a characteristic interaction between membrane-bound MAO and Δ⁹-THC can be disrupted by these chaotropic agents.     

Antibody response to Pneumocystis jirovecii major surface glycoprotein

We conducted a prospective pilot study of the serologic responses to overlapping recombinant fragments of the Pneumocystis jirovecii major surface glycoprotein (Msg) in HIV-infected patients with pneumonia due to P. jirovecii and other causes. Similar baseline geometric mean antibody levels to the fragments measured by an ELISA were found in both groups. Serum antibodies to MsgC in P. jirovecii patients rose to a peak level 3-4 weeks (p<0.001) after recovery from pneumocystosis; baseline CD4+ count > or =50 cells/microL and first episode of pneumocystosis were the principal host factors associated with this rise (both p<0.001). Thus, MsgC shows promise as a serologic reagent and should be tested further in clinical and epidemiologic studies.