Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.     

von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.

Variant von Willebrand disease designated as type I New York or type Malmö is characterized by enhanced ristocetin-induced platelet agglutination with normal von Willebrand factor multimeric distribution in plasma. We have studied four such patients belonging to three unrelated families and found in all of them a unique cytosine-to-thymine transition changing the codon for Pro503 (CCG) to Leu (CTG). In three patients the mutant allele also had a silent mutation in the codon for Ser500 (TCG-->TCA). Both nucleotide changes are present in the von Willebrand factor pseudogene; however, the characterization of distinctive markers where the gene and pseudogene differ, as well as the examination of amplified cDNA derived from platelet mRNA, confirmed that the abnormality occurs in the von Willebrand factor gene of the patients. Moreover, recombinant expression of the isolated glycoprotein Ib-binding domain of von Willebrand factor provided direct evidence that the Pro503-->Leu mutation is responsible for enhanced platelet reactivity to lower ristocetin concentrations. These results define a new structural element affecting the affinity of von Willebrand factor for glycoprotein Ib and establish the molecular basis of a variant form of von Willebrand disease.     

Evaluating candidates for kidney transplantation: some recommendations still lack convincing clinical evidence.

Sir, The paper by Zeier and Ritz in the April 2002 issue of NDT [1]is a good reminder of the importance of evaluation and selectionof kidney transplant candidates. Also, this paper clearly demonstratesthe persisting lack of clinical evidence in this field, whichhas considerable impact on large numbers of end-stage renaldisease patients. We have previously demonstrated the unexplained variations inthe evaluation     

Risk factors for placental abruption in a socio-economically disadvantaged region.

OBJECTIVE: This study was undertaken in order to determine the risk factors for pregnancies complicated by placental abruption in a socio-economically disadvantaged region in metropolitan Adelaide. METHODS: This was a retrospective case-control study including all singleton pregnancies resulting in placental abruption between 2001 and 2005. RESULTS: The overall incidence of placental abruption was 1.0%; the overall perinatal mortality among the births with abruption was 13%. Univariate analyses showed the following significant risk factors for placental abruption: preterm pre-labor rupture of the membranes (PRE-PROM; odds ratio (OR) 4.79, 95% confidence interval (CI) 1.52-15.08), non-compliance with antenatal care (OR 2.93, 95% CI 1.06-8.90), severe intrauterine growth restriction (IUGR), and elevated homocysteine levels (OR 45.55, 95% CI 7.05-458.93). Severe IUGR was significantly more common in the abruption group compared with the control group (p = 0.032). In the multivariate analysis, PRE-PROM remained a significant independent risk factor for placental abruption. Marijuana use, domestic violence, and mental health problems were more common (borderline significance) in the abruption group. Smoking and preeclampsia were not found to be associated with placental abruption in this study. CONCLUSIONS: In this high-risk population, PRE-PROM and elevated homocysteine levels appear to represent the major risk factors for placental abruption.     

Acute and long-term efficacy of oral propafenone in patients with ventricular tachyarrhythmias.

The class Ic antiarrhythmic agent propafenone was studied by repeated electrophysiologic testing in 54 patients (43 male, aged 54 +/- 10 years, mean ejection fraction of 37.3 +/- 16.9%) with ventricular tachyarrhythmias. Forty patients (74%) had coronary artery disease. Programmed ventricular stimulation (S2, S2S3 during sinus rhythm and/or during S1S1 = 500, 430, 370, and 330 ms) off antiarrhythmic drugs induced sustained ventricular tachycardia, flutter, or fibrillation in all patients. After 450-900 mg of oral propafenone/day for 4-7 days, 51 patients were restudied. In the remaining three patients, spontaneous ventricular tachycardia occurred on drug therapy. Tachycardia induction was suppressed in 9 of 51 patients restudied (18%) and rendered more difficult to induce (basic stimulation drive greater than or equal to 40 beats/min higher than at control study) in another 7 patients (14%) (overall efficacy of 31%). The tachycardia rate decreased from 220 +/- 43 to 177 +/- 44 beats/min (p less than 0.01). The right ventricular effective refractory period increased from 232 +/- 22 to 252 +/- 22 ms (p less than 0.001). Responders to propafenone therapy had higher rates of inducible ventricular tachycardia at control (greater than 230 beats/min: 43%; less than or equal to 230 beats/min: 21%; p less than 0.05), higher ejection fractions, and lower left ventricular end-diastolic pressures than nonresponders. Eleven of the 16 patients showing a positive response to propafenone therapy in electrophysiologic testing were discharged on propafenone alone. During follow-up (17 +/- 12 months), nine patients remained free from ventricular tachycardia, one patient had a relapse, and one patient died of noncardiac death.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patient-specific determinants of delay in goal-oriented patient behavior in acute myocardial infarct. Results of the post-infarct late potential study]

369 (63%) of 586 consecutive patients with confirmed myocardial infarction were admitted to hospital within 6 h of symptom onset. Patients' arrival to hospital followed a characteristic circadian distribution with a marked morning increase between 0600 and 1200 hours, and a corresponding decrease in the late night hours. There were no differences in the occurrence of late potentials and in ECG data between early and late arrival group. The early group (less than 5.9 h) was, however, characterized by significantly higher cardiac enzyme levels than the late group (greater than 6.0 h); they also experienced more arrhythmic events in the acute phase (16.0% vs. 9.7%; p less than 0.032). Catecholamines were significantly more often necessary (26.4% vs. 10.3%; p less than 0.0001). Six-month prognosis after AMI was markedly worse. The time between symptom onset and hospital arrival was not affected by age and risk factors. In univariate analysis, pain history and recurrent infarction also had no influence on delay of admission to hospital. The time interval was, however, significantly shorter when the acute event occurred during the night (18.4% vs. 8.3%; p less than 0.0001). Absence of prodromi in the prehospital phase (18.5% vs. 12.0%; p less than 0.04) and a higher socio-economic level (68.3% vs. 61.0%; p less than 0.077) also shortened the admission time, whereas a hyperactive behavioral pattern prolonged the delay time (21.1% vs. 28.9%; p less than 0.05).     

Ictal chronology and interictal spikes predict perfusion patterns in temporal lobe epilepsy: a multivariate study.

Typical (TPP) and atypical (APP) perfusion patterns (PP) may be seen in ictal SPECT of patients with temporal lobe epilepsy (TLE). APP may pose problem in the lateralization of the epileptogenic zone (EZ). We aimed to investigate predictive variables for the occurrence of TPP and APP. Fifty-one TLE patients were submitted to successful anterior-mesial temporal lobectomy. Univariate (UVA) and multivariate (MVA) analysis were performed upon clinical data, distribution of interictal spikes, and ictal chronology of seizures. From MVA, a final predictive model (FPM) was determined to better predict TPP and APP. Forty patients showed TPP (78.5%) and 11 patients APP (21.5%). Accuracy of ictal SPECT was higher in the unilateral (UIS) than in the bilateral (BIS) interictal spikes group (P = 0.05). FPM showed that patients exhibiting BIS, with shorter proportion of the electrographic seizure occurring after completion of tracer injection, and longer clinical than EEG seizure duration had more APP (P = 0.003). Generalized tonic-clonic seizures did not result in more APP. We concluded that analysis of ictal SPECT in TLE requires the knowledge of TPP and APP, the distribution of interictal spikes on temporal lobes and the ictal chronology of seizures. BIS showed that beyond a more complex epileptogenicity and seizure propagation, they may also lead to APP.