[Striction bands in a child].
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Amniotic Band Syndrome↗
Biomedical subjects
S Youssef
Publications and source records attributed to S Youssef.
[Rare complications of Meckel's diverticulum: 1. Giant Meckel's diverticulum].
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Adult↗
The potential therapeutic role of statins in central nervous system autoimmune disorders.
3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, 'statins' are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.
Animals↗
[Prognostic significance of expression of p53, bcl-2 and bax in squamous epithelial carcinoma of the larynx--a multivariate analysis].
BACKGROUND AND OBJECTIVE: Conventional clinicopathologic parameters do not accurately reflect the clinical outcome of patients with head and neck carcinoma. The establishment of additional prognostic factors that may give insight into the biologic features of a tumor is therefore an essential goal. The present study analyses the expression patterns of p53, bcl-2, and bax with regard to their relationships with conventional tumor parameters and to their prognostic significance in patients with laryngeal squamous cell carcinoma. PATIENTS/METHODS: Paraffin-embedded tissue sections of 88 primary laryngeal squamous cell carcinomas diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. The mean follow-up time was 45.9 months. RESULTS: Bcl-2 immunoreactivity was positively correlated with an advanced clinical stage, a high T category, regional lymph node metastasis, and a high histological grading. Significant relationship between clinicopathologic parameters and p53 or bax expression were not detectable. The age of the patients, advanced disease, positive bcl-2 expression, and a high level of p53 expression were significantly associated with shortened disease-specific survival in univariate analysis. In multivariate analysis, age, clinical stage, and p53 expression had independent prognostic value. CONCLUSIONS: Although expression of p53 and bcl-2 was found to be clinically relevant in univariate analysis, only p53 but not bcl-2 was an independent predictor of patient outcome. This superiority of p53 in multivariate analysis points to its central role within cell cycle and death regulation, with which it influences two important parameters of tumor progression.
Aged↗
[Intestinal invagination after vagotomy in adults].
Intestinal intussusception is a rare condition in adults. In most cases, it is caused by a benign or malignant intestinal tumor. Primitive forms are infrequent, and their occurrence following troncular vagotomoy has never been described in the literature, according to our knowledge. Two cases of post-vagotomy jejuno-jejunal intussusception are reported.
Adult↗
Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors.
The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyses the rate limiting step in cholesterol biosynthesis and is markedly inhibited by the statin family of drugs. The effect of statins on lipid lowering is clearly defined, but the ability of the drugs to directly regulate inflammatory functions has not been well explored. In this report, we show that there are differences among the statins in their capacity to induce proinflammatory responses both in human monocytes in vitro, and in leukocytes in mice in vivo. Treatment of human monocytes with lipophilic statins alone stimulated the production of MCP-1, IL-8, TNF-alpha and IL-1 beta and markedly sensitized the cells to subsequent challenge with inflammatory agents. Lipophilic statins also increased the production of reactive oxygen species in monocytes. In contrast, pretreatment of cells with the hydrophilic pravastatin did not induce these heightened inflammatory responses. Furthermore, treatment of mice with lipophilic statins caused a markedly higher influx of leukocytes into the inflamed peritoneal cavity following challenge with thioglycollate. Overall, these results demonstrate that the lipophilic statins influence a regulatory pathway in monocytes that controls cytokine production and that the statins induce different pro-inflammatory responses both in vitro and in vivo.
Animals↗
Acute appendicitis during pregnancy.
Acute appendicitis is the most common surgical emergency occurring during pregnancy. To determine possible methods for improving diagnostic and management accuracy, a retrospective review was conducted of 23 pregnant patients who underwent laparotomy with a preoperative diagnosis of acute appendicitis. Gestational stage at presentation included the first trimester in 2 patients, the second trimester in 6 patients and the third trimester in 15 patients. Eighteen patients (78.26%) had pathologically proven acute appendicitis. Perforation occurred in 2 patients. Postoperative fetal complications included one intrauterine death (4.3%) and three premature births. There was no maternal deaths and morbidity was limited to atelectasis and wound infection in 4 patients. Gestational physiologic changes make difficult the diagnosis of acute appendicitis. Prompt surgical intervention prevent maternal complications and foetal loss.
Acute Disease↗
A targeted DNA vaccine augments the natural immune response to self TNF-alpha and suppresses ongoing adjuvant arthritis.
Depending on the mode of immunization, a single administration of CFA may result in the development of a local inflammatory process or chronic poly adjuvant-induced arthritis (AA). Administration of naked DNA encoding TNF-alpha results in the generation of immunological memory to its gene product. Upon induction of AA, this memory effectively inhibited the development of disease. Self-specific Abs developed in DNA-vaccinated animals were neutralizing in vitro and could adoptively transfer the beneficial effect of the vaccine. Administration of CFA to induce a local delayed-type hypersensitivity response rather than AA did not lead to an elicited production of Abs to the gene product of the above vaccine. Thus, elicitation of protective immunity is dependent on the development of an autoimmune condition. Most importantly, the administration of the TNF-alpha DNA construct after the onset of disease led to a rapid, long-lasting remission. This suggests a highly effective way by which a DNA vaccine encoding an autologous proinflammatory cytokine can be used to reprogram the immune system to generate protective immunity to its own potentially harmful activities.
Acute Disease↗
Is there a role for endothelin antagonists in diabetic renal disease?
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Animals↗
Should malrotation in children be treated differently according to age?
PURPOSE: The aim of this study was to better define the mode of presentation, rate of volvulus, and surgical findings in children younger than 2 versus older than 2 years of age with malrotation. METHODS: The authors reviewed the charts of all patients with malrotation admitted to their hospital between January 1980 and December 1998, excluding patients having malrotation as a secondary finding. RESULTS: An upper gastrointestinal series was done in 90 patients (6% falsely negative) and a barium enema in 20 patients (40% read as normal). Fifty-eight patients had 114 associated congenital anomalies. Volvulus was found at the time of surgery in 28 patients, 5 of whom were older than 2 years. Three presented with acute symptoms and 2 with chronic symptoms. Surgery was performed by laparotomy in 103 patients and by laparoscopy in 3. Mean length of stay was 13.6 days. Mean follow-up was 19 months. Death occurred in 4 patients; postoperative bowel obstruction was seen in 3 patients (only 1 required surgery). CONCLUSIONS: Children with malrotation who are older than 2 years old have a significant risk of volvulus that is difficult to predict radiologically. They require surgical attention even if asymptomatic. Laparoscopy allows evaluation of the base of the mesentery and completion of the Ladd's procedure.
Age Factors↗
Pulmonary lymphangiectasia revisited.
PURPOSE: Pulmonary lymphangiectasia (PL) is a rare, poorly documented disease characterized by abnormal pulmonary lymphatics. Although case reports are published, little is known about survivors past the neonatal period. METHODS: This is a retrospective review of histologically proven PL in fetuses, infants, and long term survivors since 1965. RESULTS: Eleven children (8 boys, 3 girls) and 8 aborted fetuses (7 male, 1 female) were identified. The fetuses weighed 463.4 g (177 to 681 g). Six were aborted between 19 to 24 weeks of gestation for multiple malformations or anencephaly, and 2 spontaneously aborted: one with PL only, the other with twin-twin transfusion syndrome. Clinical PL was diagnosed between 0 and 11 months of age. Six children died (2 neonatal, 4 within 10 days), 5 survived. Two deaths occurred after cardiac surgery. Among survivors, the symptomatology and frequency of admissions diminished over time. Symptoms included progressive respiratory distress, chronic cough, recurrent pneumonia, bronchial asthma, and choking. One child with bilateral chylothorax was later diagnosed with Noonan syndrome; 2 patients had minor cardiac malformations. Rapid deterioration occurred with mild respiratory infections with only supportive treatment available. Chest x-ray showed marked hyperinflation with interstitial infiltrate. CONCLUSIONS: This is the first long-term study of primary PL and will help counsel parents. Although fatal in the neonatal period, survival is possible if diagnosed past the neonatal period and improvement is expected.
Abortion, Spontaneous↗
Aminoguanidine ameliorates changes in the IGF system in experimental diabetic nephropathy.
BACKGROUND: Formation of advanced glycation end-products (AGEs) has been implicated in the development of diabetic complications. As well as causing changes in structural proteins, AGEs may also alter gene expression of growth factors in vitro. The insulin-like growth factor (IGF) system, including IGF-I and modulatory IGF binding proteins (IGFBPs), is dysregulated during the development of diabetic nephropathy. METHODS: Quantitative in situ hybridization histochemistry and immunohistochemistry were used to determine the effects of aminoguanidine, an inhibitor of AGE formation, on gene expression of IGF-I and IGFBPs in kidneys of long-term (8 months duration) streptozotocin-diabetic rats. RESULTS: Diabetes was associated with increased renal expression of IGFBP-1 mRNA (diabetes 824+/-236 vs control 264+/-76 arbitrary units, P<0.01) and decreased expression of mRNAs for IGF-I (diabetes 39+/-7 vs control 185+/-23 arbitrary units, P<0.001) and IGFBP-4 (diabetes 139+/-25 vs control 383+/-54 arbitrary units, P<0.001). Aminoguanidine treatment inhibited the effects of diabetes on renal expression of mRNA for IGF-I, IGFBP-1 and IGFBP-4. The changes in IGF-I and IGFBP-1 mRNA levels were reflected in altered peptide levels. In diabetic kidneys, IGFBP-5 mRNA levels were slightly decreased to 75% of control levels (P<0.01); aminoguanidine had no effect on IGFBP-5 mRNA levels. CONCLUSIONS: These results suggest that amelioration of changes in the renal IGF system by aminoguanidine may contribute to the renoprotective effects of the latter, which have been previously shown to inhibit structural and functional aspects of diabetic nephropathy in the rat.
Animals↗
Prognostic significance of p53/bcl-2 co-expression in patients with laryngeal squamous cell carcinoma.
OBJECTIVE: The p53, bcl-2, and bax genes are known to be involved in control of cell cycle progression and regulation of apoptotic cell death. Although they are frequently altered in laryngeal squamous cell carcinoma, their clinical relevance is not yet fully understood. In the present study, individual and combined expressions of these genes were related with patient survival as well as with proliferative and apoptotic activity. DESIGN: Retrospective study. METHODS: Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. Apoptotic cells were visualized using the nick end labeling method. To assess proliferative activity of tumors, mitotic indices were determined. RESULTS: Age of patients, advanced disease (stages HI and IV), high mitotic activity, positive bcl-2 expression, high level of p53 expression, and p53/bcl-2 co-expression were significantly associated with shortened overall survival in univariate analysis. In multivariate analysis, only age and p53/bcl-2 co-expression had independent prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax ratios, were not associated with patient outcome. A significant positive correlation was found between apoptotic and mitotic activity. However, protein levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of tumor cells. CONCLUSIONS: The co-expression of p53/bcl-2 was an independent predictor of patient outcome and had a prognostic value superior to both parameters considered separately. The rate of apoptosis mainly counterbalanced proliferative activity but appeared not to be significantly influenced by p53, bcl-2, and bax.
Apoptosis↗
C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis.
Depending on the method of immunization, a single administration of CFA may result in the development of a local inflammatory process or chronic polyadjuvant-induced arthritis (AA). We administered naked DNA vaccines encoding MIP-1 alpha, MCP-1, MIP-1 beta, and RANTES to Lewis rats and confirmed that each of these vaccines induced immunological memory to the corresponding gene product. Upon induction of disease, this memory effectively inhibited the development of the autoimmune condition. Self-specific Ab's developed in DNA-vaccinated animals were neutralizing in vitro and could adoptively transfer the beneficial effect of each vaccine. Repeated administration of the constructs encoding MCP-1, MIP-1 alpha, or RANTES inhibited the development and progression of AA, even when each vaccine was administered only after the onset of disease. This suggests a highly effective way by which the immune system could be re-educated to generate protective immunity against its own harmful activities.
Animals↗
Prevention of experimental autoimmune encephalomyelitis by MIP-1alpha and MCP-1 naked DNA vaccines.
Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the central nervous system (CNS). RT-PCR verified by Southern blotting and sequencing of PCR products of two C-C chemokines, MIP-1alpha and MCP-1, was performed on brain samples from EAE rats to evaluate mRNA transcription of these chemokines at different stages of disease. mRNA transcription in of each chemokine peaked after the onset of disease and declined during its remission. Each PCR product was then used as a construct for naked DNA vaccination. The subsequent in vivo immune response to MIP-1alpha or MCP-1 DNA vaccines prevented EAE. Immunization of CFA without the encephalitogenic epitope did not elicit an anti-C-C chemokine regulatory response in DNA- vaccinated rats. Thus, modulation of EAE with C-C chemokine DNA vaccines is dependent on targeting chemokines that are highly transcribed at the site of inflammation at the onset of disease.
Amino Acid Sequence↗
Pleuropulmonary blastoma: a rare pathology with an even rarer presentation.
BACKGROUND: Pleuropulmonary blastoma is among the rarest tumors of childhood. Three types have been described: cystic, solid, and mixed. To date, bilateral disease has not been documented. METHODS AND RESULTS: A 5-week-old girl presented with a history of fever. Chest x-ray showed bilateral diffuse cystic lesions. Bowel obstruction developed that required laparotomy. Multiple small bowel polyps were resected. The patient was readmitted 4 months later with deteriorating respiratory status. She underwent sequential thoracotomies for resection of multiple bullae under high-frequency oscillatory ventilation. Small bowel polypectomies were again required because of obstruction. Lung lesions were compatible with pulmonary blastoma but could not be correlated with intestinal polyposis. Bilateral cystic renal lesions were seen on ultrasound scan. Her disease progressed, despite chemotherapy, with the appearance of metastatic iris lesions. She again underwent laparotomies for multiple recurrent generalized small bowel polyps that were causing obstruction. Expanding renal cysts affected kidney function, and she died at 14 months of age. CONCLUSIONS: The rare association between pleuropulmonary blastoma and Wilms' tumor or nephroblastomatosis is known but rarely reported. Lacking pathological evidence, we can only speculate that this was the case. We have been unable to demonstrate any histological association between the renopulmonary and digestive lesions. Despite many unanswered questions, we are likely dealing with a "syndrome" of sorts with a dire outcome, despite aggressive treatments.
Antineoplastic Combined Chemotherapy Protocols↗
Effect of diabetes and aminoguanidine therapy on renal advanced glycation end-product binding.
BACKGROUND: Advanced glycation end-products (AGEs) have been implicated in the pathogenesis of diabetic nephropathy, and aminoguanidine (AG) has been shown to decrease the accumulation of AGEs in the diabetic kidney. METHODS: This study investigates changes in AGE binding associated with diabetes in the rat kidney using in vitro and in vivo autoradiographic techniques. Male Sprague-Dawley rats were randomized into control and diabetic groups with and without AG treatment and were sacrificed after three weeks. Frozen kidney sections (20 microm) were incubated with [125I]-AGE-RNase or [125I]-AGE-BSA. To localize the AGE binding site, in vivo autoradiography was performed by injection of 15 microCi of [125I]-AGE-BSA into the abdominal aorta of the rat. RESULTS: Low-affinity binding sites specific for AGEs in the renal cortex (IC50 = 0.28 microm) were detected by in vitro autoradiography. There was a significant increase in [125I]-AGE binding in the diabetic kidney, which was prevented by AG treatment. Emulsion autoradiography revealed that binding was localized primarily to proximal tubules in the renal cortex. Renal AGE levels, as assessed by fluorescence or by radioimmunoassay, were increased after three weeks of diabetes. This increase was attenuated by AG therapy. CONCLUSIONS: AGE binding sites are present within the proximal tubules of the kidney and appear to be modulated by endogenous AGE levels. It remains to be determined if these binding sites represent receptors involved in clearance of AGEs or are linked to pathogenic pathways that lead to the development of diabetic nephropathy.
Animals↗