CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.     

Prevalence of latex sensitization and allergy in Portuguese children

The prevalence of latex allergy has been increasing not only in risk groups but also in the general population, where it is accepted to average 1%. In children, latex sensitization prevalence studies are scarce and involve different population sampling and allergy testing methods, which makes it difficult to compare across studies. Nevertheless, existing studies point towards a low prevalence of latex allergy in children, which still needs to be confirmed in the Portuguese population. Aiming at studying the prevalence of latex sensitization and allergy in a sample of Portuguese children, we studied 182 children from two different hospital outpatient clinics. A standardized questionnaire focusing on atopic background, previous history and allergic signs or symptoms on exposure to latex or fruits was given to all children and parents. Skin prick testing was performed with a battery of common aeroallergens as well as latex. Serum total IgE, Phadiatop, F x 5E and latex-specific IgE were determined in all children. Specific IgE to latex-crossreacting fruits was determined in latex-sensitized children. Based upon the questionnaire, the prevalence of latex allergy would be 0.5%. The prevalence of latex sensitization would be 3.8%, when based solely upon skin prick testing, and 12.1% (>/=0.35 IU/ml) or 6.6% (>/=0.70 IU/ml) when based singly upon determination of latex-specific IgE. When positive results for either test were considered, the prevalence of latex sensitization was 14.3%. All latex-sensitized children were atopic. Sensitivity to latex-crossreacting foodstuffs was demonstrated in 61.5% of latex-sensitized children (16/26). This study shows that the prevalence of latex allergy and sensitization in Portuguese atopic and non-atopic children, as analysed using various diagnostic methods, is similar to that observed in other countries. In addition, the assessment of latex allergy and sensitization should always include skin prick testing and determination of serum IgE.     

A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers

Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.     

Obstructive Uropathy Secondary to Ureteral Herniation in a Pediatric En Bloc Renal Graft

Ureteral herniation is a rare entity. We report the first case of extraperitoneal ureteral herniation in a pediatric en bloc renal graft causing obstructive uropathy. A 70-year-old, obese patient with an en bloc renal transplant was found to have ureterohydronephrosis in the right renal graft on magnetic resonance imaging. Nephrostomy with insertion of a double-J catheter confirmed the presence of a ureteral loop within the inguinal tract. Surgery confirmed herniation of the ureter through the internal inguinal ring, crossing over the spermatic cord. We performed release, resection, ureteral reimplantation and hernioplasty. Four months later, renal function was normal and urinary tract dilation had diminished. This case illustrates an unusual cause of obstructive uropathy in a transplanted kidney. Apart from obesity, two other factors may have contributed to its development: presence of a redundant ureter, and the fact that the ureter had been placed over, rather than under, the spermatic cord.     

Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing.     

Antithyreoglobulin und Antithyroxin

Zusammenfassung Der O<sub>2sub>-Verbrauch von mit parenteralem Thyreoglobulin längere Zeit hindurch behandelten wei&szlig;en Ratten wird stark herabgesetzt. Die Reaktionsbereitschaft solcher Tiere ist auch subcutan eingespritztem Thyroxin gegenüber vermindert, so da&szlig; der O<sub>2sub>-Verbrauch der Tiere nur auf Thyroxingaben von über 15 mg eine deutliche Steigerung zeigt. Meerschweinchen verhielten sich ähnlich wie die Ratten. Bei Kaninchen zeigte sich dagegen im Verlaufe der Thyreoglobulinbehandlung eine deutliche Steigerung des Stoffwechsels, nach der Thyreoglobulinbehandlung wurde der O<sub>2sub>-Verbrauch dieser Tiere auf Thyroxineinspritzung entsprechend erhöht. Diese an Ratten und Meerschweinchen gemachte Beobachtung dürfte ihre Erklärung darin finden, da&szlig; in diesen Versuchen das Thyreoglobulin als Antigen in serologischem Sinne wirkte, so da&szlig; ihre parenterale Verabreichung die Entstehung von gegen Thyreoglobulin und Thyroxin gerichteten Antikörpern herbeigeführt hatte. — Es ist anzunehmen, da&szlig; in diesen Versuchen das Thyreoglobulin sich als ein chemospezifisches Antigen verhielt, in dem Sinne, da&szlig; das Thyroxin neben dem Eiwei&szlig;schlepper die Rolle der spezifischen Gruppe spielte, wodurch sie die Spezifizität der entstandenen Antikörper beeinflu&szlig;t bzw. bestimmt hatte. Diese Deutung wird nicht so sehr in den Ergebnissen der mitgeteilten serologischen Versuche ihre Bekräftigung finden, vielmehr aber in der Tatsache, da&szlig; der thyroxinhemmende Faktor bei Ratten durch Sera mit thyreoglobulinvorbehandelter Tiere auch auf Normaltiere übertragbar ist, d. h. bei Ratten durch eine mit Antithyreoglobulin-Immunserum durchgeführte passive Immunisierung die O<sub>2sub>-Verbrauch-steigernde Wirkung des eingespritzten Thyroxins aufgehoben wurde.Mit 7 Textabbildungen.     

Verhandlungen Ärztlicher Gesellschaften

Ohne Zusammenfassung     

A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R−) solid organ transplant recipients

Abstract:&nbsp; Long-term prophylaxis against cytomegalovirus (CMV) started immediately after transplantation in (D+/R&minus;) poses a higher risk of late-onset CMV disease. Delayed CMV prophylaxis could allow a transitory exposure of the immune system to CMV, which would let the immune system mount an adequate CMV-specific cytotoxic response in (D+/R&minus;) patients and confer protection against CMV disease. We included all (D+/R&minus;) solid organ transplant recipients (SOT) performed at our institution (January 3/October 6) who received CMV prophylaxis (mainly with oral valganciclovir) during 100&nbsp;d. In the first period (until December 4), prophylaxis was initiated immediately after transplantation (conventional prophylaxis: CP). Since January 5, it was initiated after 14&nbsp;d (delayed prophylaxis: DP). Incidence and severity of CMV disease was compared between both groups. A total of 44 SOT recipients were included (CP: 26 and DP: 18). CMV disease was diagnosed in eight patients (18%), seven of 26 (27%) in the CP group, and one of 18 (5.5%) in the DP group (p&nbsp;=&nbsp;0.07). CMV colitis was reported in five of 26 patients in the CP group (19%), whereas there were no cases of visceral CMV disease in the DP group (p&nbsp;=&nbsp;0.048). A 14-d delay in the beginning of long-term prophylaxis against CMV in (D+/R&minus;) is safe and could prevent the onset of late-CMV disease.