Oncogenic CARMA1 couples NF-κB and ß-catenin signaling in diffuse large B-cell lymphomas.

Constitutive activation of the antiapoptotic nuclear factor-κB (NF-κB) signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL). Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of ß-catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3ß to oncogenic CARMA1. Recruitment of the ß-catenin destruction complex was independent of CARMA1-BCL10-MALT1 complex formation or constitutive NF-κB activation and promoted the stabilization of ß-catenin. The ß-catenin destruction complex was also recruited to CARMA1 in ABC DLBCL cell lines, which coincided with elevated ß-catenin expression. In line, ß-catenin was frequently detected in non-GCB DLBCL biopsies that rely on chronic BCR signaling. Increased ß-catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF-dependent transcriptional activation in response to WNT signaling. In conjunction with NF-κB, ß-catenin enhanced expression of immunosuppressive interleukin-10 and suppressed antitumoral CCL3, indicating that ß-catenin can induce a favorable tumor microenvironment. Thus, parallel activation of NF-κB and ß-catenin signaling by gain-of-function mutations in CARMA1 augments WNT stimulation and is required for regulating the expression of distinct NF-κB target genes to trigger cell-intrinsic and extrinsic processes that promote DLBCL lymphomagenesis.

Chronic recurrent multifocal osteomyelitis associated with Crohn's disease.

Chronic recurrent multifocal osteomyelitis (CRMO) was first described by Giedion in 1972 as a self-limited relapsing noninfectious inflammatory condition usually affecting children and adolescents. The association of CRMO with psoriasis, palmoplantar pustulosis, and SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) has been described. In this case report, we present a 49-year-old man with CRMO coexisting with Crohn's disease. To our knowledge, this is the first report of CRMO with Crohn's disease without the presence of pustular skin lesions or other features of SAPHO syndrome.

Salicylate toxicity in the older patient.

Nonacetylated salicylates are frequently used in the treatment of musculoskeletal complaints and pain management in older patients because of their possible lower gastrointestinal and renal toxicity as compared with other nonsteroidal anti-inflammatory agents. We report five patients with chronic salicylate intoxication seen at the Atlanta VA Medical Center. All charts of patients diagnosed with salicylate toxicity were reviewed, and cases with acute, intentional intoxication were excluded. In the study group, three patients took a nonacetylated salicylate, the other two took an acetylated salicylate. Our patients ranged in age from 51 to 78 years old. One patient died of respiratory failure and "sepsis-like syndrome," a potentially lethal complication of salicylate toxicity. Four of the patients had altered mental status as a presenting complaint. The presence of a combined respiratory alkalosis and metabolic acidosis, present in all five patients, was the clue for diagnosis in three of the cases. Tinnitus was reported in only one patient. A significantly decreased urate level and a wide anion gap were consistent findings as well. Two of the patients improved after hydration and discontinuation of use of the drug, two required alkalinization of the urine, and one required dialysis. Clinicians need to be more aware of the potential toxicity, including life-threatening complications, with the use of salicylates, particularly in high risk populations such as elderly patients and patients with multiple medical problems.

Tamponade in patients undergoing cardiac surgery: a clinical-echocardiographic diagnosis.

The purpose of this study was to evaluate the sensitivity of current echocardiographic criteria in detecting cardiac tamponade in the patient who has undergone cardiovascular surgery. Because the current echocardiographic criteria for tamponade were initially developed and studied predominantly in patients with medical problems, relatively less information is available in patients who have undergone cardiac surgery. Of 848 consecutive patients who underwent cardiovascular surgery, patients were selected for the study if they had clinical or hemodynamic deterioration and had undergone an echocardiogram just before a successful pericardiocentesis or a surgical evacuation of pericardial blood or clot. The echocardiograms were evaluated for evidence of chamber collapse, cardiac motion, Doppler flow variations, and the location and width of pericardial separation. Fourteen patients were identified who met the inclusion criteria (clinical or hemodynamic deterioration, recent echocardiogram, and successful intervention) for cardiac tamponade. The clinical and hemodynamic findings were hypotension (13 patients), low cardiac output (7), low urine output (3), cardiopulmonary arrest (1), elevated central venous pressure (1), and shortness of breath (1). In these patients current echocardiographic criteria were seen infrequently: chamber collapse in the right atrium (6 of 14 patients) and right ventricle (4 of 14); Doppler flow variation (2 of 5); and swinging heart (0 of 15), whereas increased pericardial separation (> or = 10 mm) was seen in all (14 of 14) the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

On early surgery of hydrocephalus in low-birth-weight infants.

The paper weighs the indication and the timing of surgery in hydrocephalus mostly due to ventricular haemorrhage in premature infants with an average of 31 weeks of gestational age and of 1.409 g average birth weight. The authors suggest to wait with the intervention until the intraventricular haemorrhage has subsided because the hypertension may often cease when the CSF is not bloody anymore. In case of a progressive process they gained favourable results with early surgery. They give a detailed account about the choice of the various shunts, list eventual complications, the US and CT controls.

Congenital short colon associated with imperforate anus (Zachary-Morgan syndrome).

Two cases of short colon with imperforate anus are presented. Terminal colostomy is the therapy of choice in the neonatal period. As the definitive final procedure, trimming into a tubular structure and abdomino-perineal pull-through operation is suggested. A survey is given of similar cases reported in the literature.

Metabolic relations of serum lipids and lipoproteins in diabetic children.

Serum lipids and lipoproteins of 29 insulin dependent diabetic children have been determined and related to the metabolic status of the patients. The findings were compared to results obtained in 30 healthy children. The diabetic children showing unsatisfactory metabolic parameters had significantly higher total lipid and total triglyceride levels than did the healthy children (p less than 0.01). All diabetic children, independently of their metabolic status, exhibited an increased low density lipoprotein cholesterol level (p less than 0.01). On the other hand, high density lipoprotein cholesterol levels found in diabetics did not differ from normal values and showed no relationship with their metabolic status. Prevention of vascular complications of diabetes must be started in childhood by attentive care directed to all details of the pathomechanism.

Reflex bradycardia: a grave complication of oesophageal atresia repair.

Among 39 infants operated upon for oesophageal atresia in newborn age, 5 presented attacks of reflex bradycardia during meals. One patient died at the age of one and a half years. Four patients became symptom-free on atropine treatment. They are healthy and develop satisfactorily.

Mesenteric vascular occlusion in infants and children: report of two cases and review of the literature.

Mesenteric vascular occlusion is a rare disease in the paediatric age group. The pertaining literature is reviewed and two cases are reported. In the first one the vascular obstruction developed after a Wilms tumour on the right side had been removed. Following bowel resection and end-to-end anastomosis the patient died of uraemia. Post mortem examination revealed a diffuse membranous glomerulonephritis and pseudoxanthomatosis in the remaining left kidney, the function of which had probably been affected by the shock associated with mesenteric thrombosis. In the second case a mixed mesenteric vascular occlusion was found without any previous disease; after ileal resection and ileo-coecal anastomosis the baby made a smooth recovery.

Treatment of neonatal abdominal cysts.

Intraperitoneal or retroperitoneal cystic structures in the newborn appear with a variable clinical picture and in the case of intra-abdominal cysts, surgery is performed mostly on an emergency basis. In such cases the exact preoperative diagnosis is difficult and is seldom made. With early laparotomy, extensive small bowel resection can usually be avoided. Retroperitoneal lesions are mostly of renal origin; in such cases, preoperative diagnosis is easy, being based on specific examinations. In the year 1973, 5 newborns with an intraperitoneal or retroperitoneal cyst have been treated surgically. In this series, one infant died after resection of 90% of the small bowel.