The effect of corticosteroids and other antineoplastic agents on the generation of leukocyte migration inhibition factor

We have shown that hydrocortisone in physiological concentrations can inhibit the production of leukocyte migration inhibition factor (LMIF), but does not diminish the action of this lymphokine. Other agents tested failed to influence LMIF production. Inhibition of LMIF production by corticosteroids was influenced by the nature of the stimulus used for the production as an effect could be seen with PHA or Con A, but not Staphylococcal enterotoxin A (SEA). Production of LMIF was promptly restored after removal of the steroids. Furthermore, addition of a calcium ionophore to PHA restored the production of LMIF even in the presence of corticosteroids. In contrast, addition of exogenous IL-2 did not correct the defect in lymphokine secretion. We believe that inhibition of the production of LMIF by steroid may lead to defective granulocytic function and thus, predispose to infection.     

Consanguineous Iranian kindreds with severe Tourette syndrome

The search for vulnerability genes for Tourette syndrome has been ongoing for nearly three decades. The contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. Homozygosity mapping has been successfully used to detect recessive loci within populations with high rates of consanguinity. Using this technique, even quite small inbred families can be informative due to autozygosity in which the two alleles at an autosomal locus are identical by descent (i.e., copies of a single ancestral gene). To explore the utility of this approach, we identified 12 consanguineous Iranian families. Remarkably, these families were seen with an unusual natural history characterized by the early onset of vocal tics and coprolalia and frequent comorbidity with obsessive‐compulsive disorder. Genotyping the affected and unaffected members of these pedigrees has the potential to identify rare recessive contributions to this disorder. © 2008 Movement Disorder Society     

Effect of acetyl salicylic acid on production and action of leukocyte-derived interferons.

Although acetylsalicylic acid does not itself induce interferon, acetylsalicylic acid was found to significantly enhance the production of both human alpha interferon and human gamma interferon when added with the appropriate inducers to cultures of human peripheral blood mononuclear cells. The mechanisms associated with this effect were investigated.     

Value of gadolinium-enhanced magnetic resonance imaging in patients with Tako-Tsubo-like left ventricular dysfunction.

We present gadolinium-enhanced cardiac magnetic resonance imaging (CMRI) in Tako-Tsubo-like left ventricular dysfunction showing the findings in acute phase and in follow-up. Gadolinium-enhanced CMRI allows to distinguish between myocardial infarction and other myocardial alterations, e.g., myocarditis. CMRI may thus permit to non-invasively identify patients with Tako-Tsubo syndrome by ruling out myocardial infarction or myocarditis in the setting of wall motion abnormalities (WMA).     

The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activation

In vitro studies indicate that binding of talin to the beta(3) integrin cytoplasmic domain (tail) results in integrin alpha(IIb)beta(3) (GPIIb-IIIa) activation. Here we tested the importance of talin binding for integrin activation in vivo and its biological significance by generating mice harboring point mutations in the beta(3) tail. We introduced a beta(3)(Y747A) substitution that disrupts the binding of talin, filamin, and other cytoplasmic proteins and a beta(3)(L746A) substitution that selectively disrupts interactions only with talin. Platelets from animals homozygous for each mutation showed impaired agonist-induced fibrinogen binding and platelet aggregation, providing proof that inside-out signals that activate alpha(IIb)beta(3) require binding of talin to the beta(3) tail. beta(3)(L746A) mice were resistant to both pulmonary thromboembolism and to ferric chloride-induced thrombosis of the carotid artery. Pathological bleeding, measured by the presence of fecal blood and development of anemia, occurred in 53% of beta(3)(Y747A) and virtually all beta(3)-null animals examined. Remarkably, less than 5% of beta(3)(L746A) animals exhibited this form of bleeding. These results establish that alpha(IIb)beta(3) activation in vivo is dependent on the interaction of talin with the beta(3) integrin cytoplasmic domain. Furthermore, they suggest that modulation of beta(3) integrin-talin interactions may provide an attractive target for antithrombotics and result in a reduced risk of pathological bleeding.     

Patients' tolerance and early complications of transrectal sonographically guided prostate biopsy: prospective study of 300 patients

PURPOSE: To determine the degree of pain and discomfort associated with transrectal sonography (TRS)-guided biopsy of the prostate and to analyze the complications associated with this procedure. METHODS: Three hundred men referred as part of an investigation to exclude prostate cancer were studied. The reasons for referral were suspected prostate cancer due to increased serum prostate-specific antigen level (>4 ng/ml), the finding of a palpable nodule or greater firmness of one prostatic lobe than the other on digital rectal examination, or the finding of a suspicious area of neoplasm of the prostate on TRS biopsy. All TRS-guided biopsies were performed as outpatient procedures without anesthesia. Ciprofloxacin prophylaxis was used in all patients before biopsy. Tolerance of the procedure was recorded immediately after the examination and graded on a scale of 0-4 as follows: 0, no pain; 1, very mild pain; 2, moderate pain; 3, severe pain; 4, intolerable pain. Complications recorded in the first week after the procedure were analyzed. They included mild pain, self-limiting hematuria, hematospermia, rectal bleeding, severe hematuria, septicemia, severe hemorrhage of the anus, and vasovagal attack. RESULTS: Out of 300 TRS-guided biopsies, 10 early complications were recorded. The most frequent was septicemia, which was seen in 5 cases (1.7%). Hematuria occurred in 29 patients, 3 of which were severe. Rectal bleeding and vasovagal attack occurred in 1 patient each. All patients made a full recovery with appropriate conservative management. Ten cases (3.33%) of severe pain (grade 3) and intolerable pain (grade 4) were observed. Three out of these 10 patients completed the procedure. The procedure was terminated in 1 patient, and 6 patients required local anesthetic due to perianal disease. CONCLUSIONS: TRS-guided prostate biopsy can be performed without local anesthesia in 90% of patients. Prophylactic antibiotics are mandatory to minimize approximately infectious complications.