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Biomedical subjects

A Lerner

Publications and source records attributed to A Lerner.

At least 55 records · Page 3Linked to original sources
PubMed1998

Type 4 cyclic adenosine monophosphate phosphodiesterase as a therapeutic target in chronic lymphocytic leukemia.

Theophylline, a drug known to inhibit several classes of adenosine 3'5' cyclic monophosphate (cAMP) phosphodiesterases (PDEs), induces apoptosis in chronic lymphocytic leukemia (CLL) cells. Because the PDE target for theophylline in CLL remains unknown, we examined the ability of isoform-specific PDE inhibitors to increase cAMP levels and induce apoptosis in primary CLL cells. Reverse transcriptase-polymerase chain reaction of purified CLL cDNA amplified transcripts for PDE1B, 4A and 4B. The type 4 PDE inhibitor rolipram but not the type 1 inhibitor vinpocetine increased CLL cAMP levels. Rolipram-inhibitable (type 4) but not calcium-calmodulin augmented (type 1) PDE enzyme activity was detected in CLL samples. In samples from 13 of 14 CLL patients, rolipram induced apoptosis in a dose-dependent fashion over a 48-hour period. Interleukin-2 (IL-2)-cultured whole mononuclear cells (WMC) and anti-Ig stimulated CD19(+) B cells were resistant to the induction of apoptosis by rolipram while unstimulated CD19(+) B cells, which had a high basal apoptotic rate, were more sensitive. Rolipram stimulated elevations in cAMP levels in all four of these cell populations, suggesting that they differed in sensitivity to cAMP-induced apoptosis. Consistent with this hypothesis, incubation with the cell permeable cAMP analog dibutyryl-cAMP induced apoptosis in CLL cells and unstimulated B cells but not in IL-2-cultured WMC or anti-Ig stimulated B cells. These data identify PDE4 as a family of enzymes whose inhibition induces apoptosis in CLL cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis.

We report four patients with cystic fibrosis and fulminant Clostridium difficile-associated colitis: two died, and one required hemicolectomy. Three of four patients carried the N1303K mutation. Severe and fatal C. difficile colitis can occur in cystic fibrosis patients, possibly with a genotype-specific predilection (i.e., N1303K/other). Because cystic fibrosis patients may have a wide spectrum of gastrointestinal symptoms, disease caused by C. difficile must be considered when these patients have acute abdominal pain, diarrhea, or severe leukocytosis.

Child↗
PubMed1998

Increased prevalence of autoantibodies in celiac disease.

Several features suggest an immune mechanism operates in celiac disease. Information on the autoantibody repertoire in this condition is lacking. The purpose of the study was to investigate the reactivity of celiac patients sera to various autoantigens widely distributed in the human intestine. Seventy children, celiacs and controls, were evaluated for serum autoantibodies using ELISA and immunofluorescence. Celiac patients had increased prevalence of serum anti-single-stranded DNA (14%), anti-double-stranded DNA (23%), anti-cardiolipin (14%), and anti-endomysial autoantibodies (63%). The relevance of this finding on the extraintestinal manifestations of celiac disease or the coexistence of autoimmune conditions and celiac disease remains to be determined.

Autoantibodies↗
PubMed1998

Olanzapine treatment in patients with typical and atypical neuroleptic-associated agranulocytosis.

Two cases are reported of patients who developed agranulocytosis after treatment with typical and atypical antipsychotics. The patients were successfully treated with olanzapine. We suggest the consideration of olanzapine as a safer treatment in patients who require immediate continuation of antipsychotic medication and have a prior history of classic and atypical neuroleptic-induced agranulocytosis.

Adult↗
PubMed1998

Ilizarov external fixation in the management of bilateral, highly complex blast injuries of lower extremities: a report of two cases.

Because of their complexity, war injuries inflicted by a blast mechanism often require tailoring of treatment to attain a more individualized solution. We report two cases of bilateral, severely mangled lower limbs with open tibial fractures and crush injuries to the feet. In each case, one limb had to be amputated below the knee, but the other limb was saved by immediate stabilization in a tubular external fixation frame crossing the knee; the frame was later replaced by a hybrid ring fixation frame with a freely moving knee. Such incidences are rare, and the particular management detailed here has not previously been reported in the literature.

Adult↗
PubMed1998

CSF levels of carnitine in children with meningitis, neurologic disorders, acute gastroenteritis, and seizure.

Carnitine concentrations in CSF, serum, and urine in normal febrile children and children with meningitis, neurologic disorders, and dehydration were studied. Carnitine levels in CSF were 1/10 compared with serum in normal febrile children. These levels increased two- to three-fold in the pathologic conditions studied. Since damage to the blood-brain barrier occurs in these conditions, higher blood-brain barrier permeability might explain CNS carnitine accumulation.

Adolescent↗
PubMed1998

Fisics-Incor bovine pericardial bioprostheses: 15 year results.

BACKGROUND: From March 1982 to December 1995, 2,607 Fisics-Incor bovine pericardial bioprostheses were implanted in 2,259 patients. Mean age was 47.2 +/- 17.5 years, and 55% were male. Rheumatic fever was present in 1,301 (45.7%) patients. METHODS: One thousand and seventy-three aortic valve replacements, 1,085 mitral replacements, 27 tricuspid replacements, 195 mitral-aortic replacements, and 16 other combined valve replacements were carried out. Combined procedures were performed in 788 (32.9%) patients, the most frequent being tricuspid valve repair (9.2%) and coronary artery bypass grafting (7.7%). RESULTS: Hospital mortality was 8.6% (194 patients), 8.6% for the mitral group, 4.7% for the aortic group, and 12.8% for double-valve replacements. The linear rates for calcification, thromboembolism, rupture, leak and endocarditis were, respectively, 1.1%, 0.2%, 0.9%, 0.1% and 0.5% patient-year. The actuarial survival curve was 56.7 +/- 5.4% in 15 years. Survival free from endocarditis was 91.92%, survival free from thromboembolism was 95 +/- 1.7%, survival free from rupture was 43.7 +/- 9.8%, survival free from leak was 98.9 +/- 4.5%, and survival free from calcification was 48.8 +/- 7.9% in 15 years. In the late postoperative period, 1,614 (80.6%) patients were in New York Heart Association functional Class I. CONCLUSIONS: We conclude that the results with the Fisics-Incor bovine pericardial prostheses were satisfactory in our group of patients.

Adult↗
PubMed1998

Transthyretin: a marker for celiac disease activity.

Transthyretin (TTR), a well-established nutritional marker, was measured in patients with active and inactive celiac disease (CD) in order to assess its value as a marker of disease activity. CD activity was assessed by intestinal biopsy to determine intestinal atrophy histologically and by measuring the level of antiendomysial antibody titer. TTR was measured in 26 CD patients fed a diet containing gluten and 22 CD patients fed a gluten-free diet. The control group was composed of 65 healthy sex- and age-matched children. We compared the TTR levels to the two established markers of CD activity. TTR levels were lowest among the celiac patients fed a diet containing gluten and differed significantly from those of the other two groups (r = 0.7, p < 0.002). The TTR levels correlated inversely with both the degree of mucosal atrophy (r = 0.6, p < 0.005) and with anti-endomysial antibody titers (p < 0.005). TTR levels appear to be correlated with morphologic and serologic markers of activity in celiac patients. TTR can be used as a systemic parameter in assessing celiac patients. It can contribute information to the evaluation of children in whom celiac disease is suspected, and it can monitor patients' diet compliance.

Adolescent↗
PubMed1998

S-adenosylmethionine decarboxylase activity and utilization of exogenous putrescine are enhanced in colon cancer cells stimulated to grow by EGF.

UNLABELLED: Polyamines spermidine and spermine and their precursor putrescine are necessary for cell growth. Polyamine content is high in rapidly growing malignant cells, due to enhanced putrescine synthesis by ornithine decarboxylase (ODC), and increased uptake. In contrast to other cells of the body, colon cancer cells are exposed to high putrescine concentrations from the lumen. AIMS: To investigate the utilization of luminal putrescine in colon cancer, we studied the effect of a potent mitogen, epidermal growth factor (EGF), on the activity of the enzyme responsible for putrescine conversion, S-adenosylmethionine decarboxylase (SAMDC), in Caco-2 cells. METHODS: Cell counts, ODC and SAMDC activities and intracellular polyamines were evaluated in the presence and absence of exogenous putrescine in concentrations resembling those normally present in the colonic lumen. RESULTS: ODC and SAMDC activity and putrescine uptake were strongly stimulated by EGF. Both synthesized and absorbed putrescine was rapidly converted to spermidine and spermine after EGF. Conversion pattern was identical in the cells stimulated with EGF only and EGF plus exogenous putrescine, indicating that, if stimulated to proliferate, colon cancer cells utilize the entire available putrescine pool. SAMDC inhibitor, methylglyoxal-bis-guanylhydrazone, induced growth arrest which was not reversed by exogenous putrescine, but only by high concentrations of spermidine. CONCLUSION: Enhanced proliferation in colon cancer cells is associated with increased SAMDC activity and rapid conversion of putrescine to spermidine and spermine. SAMDC might be a preferable target for therapeutic attempts to impair growth by reducing intracellular polyamine pools in colon cancer.

Adenosylmethionine Decarboxylase↗
PubMed1997

Gallbladder pseudopolyp formation following percutaneous liver biopsy.

Following an unsuccessful liver biopsy in a 16-year-old girl in which only bile was obtained, a sonographic (US) study was performed. The findings were those of free fluid just adjacent to the gallbladder as well as a small intraluminal protrusion of the gallbladder wall. The US features of the gallbladder finding were consistent with a polyp. Gallbladder polyps are very rare in children, however, sporadic case reports do exist. An US study 24 h after the invasive procedure revealed complete regression of the free fluid; the gallbladder wall protrusion has disappeared. We suggest that the tip of the biopsy needle had penetrated the gallbladder wall and caused a bile leak. The needle penetration caused elevation of the inner wall layer at the entrance site, which was indistinguishable from the sonographic findings of a gallbladder polyp [1-4]

Adolescent↗
PubMed1997

Gallbladder polyps in children: a rare condition.

Although gallbladder polyps are well documented in adults, only three cases in children have been reported in the literature. We present two pediatric cases in which gallbladder polyps were detected by ultrasound, confirming this as the imaging method of choice in diagnosing gallbladder disease.

Child↗