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M Ehrlich

Publications and source records attributed to M Ehrlich.

At least 55 records · Page 3Linked to original sources
PubMed1999

Frequent hypomethylation in Wilms tumors of pericentromeric DNA in chromosomes 1 and 16.

Rearrangements in the pericentromeric heterochromatin of chromosome 1 or 16 are often found in many types of cancers, including Wilms tumors, and have been suggested to contribute to oncogenesis or tumor progression. The oncogenic potential of these rearrangements has been ascribed to the resulting chromosome arm imbalances affecting the dosage of tumor suppressor genes or protooncogenes. Because DNA hypomethylation has been linked to rearrangements in the pericentromeric regions of chromosome 1 and 16 in two types of non-cancer cell populations, we examined methylation of normally highly methylated satellite DNA sequences in these regions in Wilms tumors. Hypomethylation was found to be frequent in juxtacentromeric (satellite 2) sequences and, especially, in centromeric (satellite alpha) sequences of chromosome 1. Hypomethylation of satellite 2 DNA of chromosome 16 showed a high degree of concordance with that of satellite 2 DNA of chromosome 1. We discuss the relationship of this satellite DNA hypomethylation in Wilms tumors to chromosome aberrations, as determined by assays for loss of heterozygosity.

Centromere↗
PubMed1999

Cerebral oxygenation during cardiopulmonary bypass measured by near-infrared spectroscopy: effects of hemodilution, temperature, and flow.

OBJECTIVE: To determine the effects of hemodilution, PaCO2, PaO2, arterial pressure, and temperature on cerebral oxygenation during mild hypothermic cardiopulmonary bypass (CPB). PARTICIPANTS: Fourteen patients electively scheduled for cardiac surgery. INTERVENTIONS: Oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), hemoglobin differential (Hb-diff = HbO2-Hb), and oxidized cytochrome aa3 (CtO2) were measured with near-infrared spectroscopy (NIRS) during CPB. RESULTS: With onset of CPB, a significant decrease in HbO2 (median, -4.55 micromol/L; 25th to 75th percentile, -5.5 to -3.1; p < 0.05), Hb-diff (median, -3.88 micromol/L; 25th to 75th percentile, -4.7 to -1.9; p < 0.05), and CtO2 (median, -0.05 micromol/L; 25th to 75th percentile, -0.15 to 0; p < 0.001) occurred. The simultaneous decrease in arterial hemoglobin concentration (from 11.7 to 8.5 g/100 mL, p < 0.005) correlated significantly with changes in HbO2 (r2 = 0.71; p < 0.001), Hb-diff (r2 = 0.59; p < 0.005), and CtO2 (r2 = 0.57; p < 0.005). After 24 minutes of CPB, the largest decline in HbO2 (-5.03 micromol/L) and Hb-diff (-5.68 micromol/L) was recorded, whereas CtO2 showed no changes during cooling. During CPB, Hb and Hb-diff significantly correlated with the duration of CPB, PaO2 and PaCO2. CONCLUSIONS: In early stages of CPB, a diminished cerebral oxygen supply was found, which may be caused by acute hemodilution. Despite an increased extraction of oxygen as demonstrated by the decrease in Hb-diff, cerebral energy balance reflected by CtO2 was maintained within a safe range during cooling. Because NIRS measures regional cerebral oxygenation, it is useful as an adjunct to global measures in the early noninvasive detection of cerebral hypoxia.

Blood Pressure↗
PubMed1999

A comparison of the monitors INVOS 3100 and NIRO 500 in detecting changes in cerebral oxygenation.

BACKGROUND: Measurements of cerebral haemoglobin oxygenation of 2 near-infrared spectroscopy devices (INVOS 3100 and NIRO 500) were compared during and after hypocapnia. METHODS: Fifteen awake, healthy volunteers, who hyperventilated to obtain end-tidal CO2 (EtCO2) values of approximately 20 mmHg, were studied. During hyperventilation and 8 min thereafter, EtCO2, INVOS 3100 (RSO2 = regional cerebral oxygenation) and NIRO 500 recordings (HbO2 = oxyhaemoglobin, Hb = deoxyhaemoglobin, Hb-diff = HbO2-Hb, CtO2 = oxidised cytochrome oxidase aa3) were analysed. RESULTS: Hyperventilation induced a significant decline in EtCO2 from 30.5 to 14.7 mmHg (P < 0.001) and RSO2 from 67.1% to 62.7% (P = 0.025). At hypocapnia, only Hb (+1.61 +/- 0.48 mumol/L; P < 0.001) and Hb-diff (-3.01 +/- 2.0 mumol/L; P < 0.001) indicated a decline in cerebral haemoglobin oxygenation. Within 8 min after hyperventilation, both EtCO2 and RSO2 normalised to values insignificantly different from baseline. In contrast, Hb and Hb-diff remained significantly different (Hb: +2.52 +/- 1.28 mumol/l; P < 0.001, Hb-diff: -4.31 +/- 4.0 mumol/L; P < 0.001). A correlation with EtCO2 was found for RSO2 (R = 0.35; P < 0.001) and CtO2 (R = 0.42; P < 0.001). All volunteers were continuously awake and none presented clinical symptoms of cerebral hypoxia. CONCLUSION: Changes in cerebral haemoglobin oxygenation state were reflected more accurately by INVOS 3100 than NIRO 500. The cause may be the different technology of the monitors, since INVOS 3100 eliminates the contribution of extracranial oxygenation.

Adult↗
PubMed1998

Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.

BACKGROUND: Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single center's experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS: From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS: One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION: HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.

Adult↗
PubMed1998

Perioperative risk factors for mortality in patients with acute type A aortic dissection.

BACKGROUND: Patients with acute type A aortic dissection are associated with a high mortality rate and postoperative complications. This study was designed to explore perioperative risk factors for death in patients with acute type A aortic dissection. METHODS AND RESULTS: One hundred nine consecutive surgical patients with acute type A aortic dissection were included in the present study. Thirty-five perioperative risk factors were used in the statistical analysis for mortality prediction. The 30-day mortality rate for all patients was 30% (33 of 109). Univariate analysis revealed 5 preoperative and intraoperative risk factors that were found to be statistically significant predictors for death: older age, renal failure, preoperative hemodynamic instability, preoperative cardiopulmonary resuscitation, and lack of retrograde cerebral perfusion (P < 0.05). Rupture of aneurysm, hypothermic circulatory arrest time, and operation date were not found to be risk factors for death. Stepwise multiple logistic regression confirmed that older age and lack of retrograde cerebral perfusion were statistically significant independent risk factors for death (P < 0.05). Four postoperative complications were found to be statistically significant prognostic indicators for death: liver failure, stroke, sepsis, and reoperation after the initial surgery (P < 0.05). CONCLUSIONS: Perioperative risk factors for death after the operation for acute type A aortic dissection were identified. This will allow physicians and surgeons to better assess the patient's risk, which will lead to better outcome.

Acute Disease↗
PubMed1998

Hypomethylation of pericentromeric DNA in breast adenocarcinomas.

Drug-induced DNA demethylation in normal human cells and inherited localized hypomethylation in mitogen-stimulated lymphocytes from patients with a rare recessive disease (ICF: immunodeficiency, centromeric region instability, facial anomalies) are associated with karyotypic instability. This chromosomal recombination is targeted to heterochromatin in the vicinity of the centromere (pericentromeric region) of human chromosome 1. Pericentromeric rearrangements in this chromosome as well as overall genomic hypomethylation are frequently observed in many kinds of cancer, including breast adenocarcinoma. We found that almost half of 25 examined breast adenocarcinomas exhibited hypomethylation in satellite 2 DNA, which is located in the long region of heterochromatin adjacent to the centromere of chromosome 1 and is normally highly methylated. One of the 19 examined non-malignant breast tissues displaying fibrocystic changes was similarly hypomethylated in this satellite DNA. We also looked at an opposing type of methylation alteration in these cancers, namely, hypermethylation in a tumor-suppressor gene region that is frequently hypermethylated in breast cancers. We found that increased methylation in the E-cadherin promoter region and decreased methylation in satellite 2 DNA were often present in the same breast cancers. While hypermethylation in certain tumor-suppressor gene regions may favor tumorigenesis by repressing transcription, demethylation of other DNA sequences may predispose to cancer-promoting chromosomal re-arrangements.

Adenocarcinoma↗
PubMed1998

A dominant negative mutant of the insulin-like growth factor-I receptor inhibits the adhesion, invasion, and metastasis of breast cancer.

The 5-year survival rate for women with metastatic breast cancer is only 25-30%; thus, the need to improve treatment is apparent. Overexpression of insulin-like growth factor-I receptor (IGF-IR) correlates with poor prognosis and local recurrence. In this study, we addressed whether functional impairment of IGF-IR affects adhesion, invasion, and metastasis of breast cancer. Impairment of IGF-IR function was achieved by transfecting a dominant negative form of the receptor, termed 486stop, into MDA-MB-435 metastatic breast cancer cells. The protein product of 486stop is secreted extracellularly, resulting in a bystander effect. Cellular adhesion to laminin and collagen was inhibited 94 and 88%, respectively. Furthermore, 486stop inhibited insulin-like growth factor-I-stimulated invasion through collagen IV by 75%. The dominant negative receptor was secreted, as evidenced by the observation that MDA-MB-435 and MDA-MB-231 cells were prevented from binding to laminin by 90% when treated with conditioned medium (CM) from 486stop-transfected cells. CM also inhibited the invasion of MDA-MB-231 cells across collagen IV by 80%. Finally, CM made MDA-MB-231 cells 30% more sensitive to Taxol-induced cell death. Growth in soft agar was suppressed by 486stop, but growth in monolayer was unaffected. When injected into the mammary fat pad, 486stop did not significantly suppress growth of the primary tumor, but metastasis to the lungs, livers, lymph nodes, and lymph vessels was significantly decreased compared to the vector control. In conclusion, inhibition of IGF-IR resulted in suppression of adhesion, invasion, and metastasis, providing a mechanistic rationale for targeting IGF-IR in the treatment of metastatic breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Neuronal defects and delayed wound healing in mice lacking fibroblast growth factor 2.

Basic fibroblast growth factor (FGF2) is a wide-spectrum mitogenic, angiogenic, and neurotrophic factor that is expressed at low levels in many tissues and cell types and reaches high concentrations in brain and pituitary. FGF2 has been implicated in a multitude of physiological and pathological processes, including limb development, angiogenesis, wound healing, and tumor growth, but its physiological role is still unclear. To determine the function of FGF2 in vivo, we have generated FGF2 knockout mice, lacking all three FGF2 isoforms, by homologous recombination in embryonic stem cells. FGF2(-/-) mice are viable, fertile and phenotypically indistinguishable from FGF2(+/+) littermates by gross examination. However, abnormalities in the cytoarchitecture of the neocortex, most pronounced in the frontal motor-sensory area, can be detected by histological and immunohistochemical methods. A significant reduction in neuronal density is observed in most layers of the motor cortex in the FGF2(-/-) mice, with layer V being the most affected. Cell density is normal in other regions of the brain such as the striatum and the hippocampus. In addition, the healing of excisional skin wounds is delayed in mice lacking FGF2. These results indicate that FGF2, although not essential for embryonic development, plays a specific role in cortical neurogenesis and skin wound healing in mice, which, in spite of the apparent redundancy of FGF signaling, cannot be carried out by other FGF family members.

Animals↗
PubMed1998

Islet injury induces neurotrophin expression in pancreatic cells and reactive gliosis of peri-islet Schwann cells.

Pancreatic islets are enveloped by a sheath of Schwann cells, the glial cells of the peripheral nervous system (PNS). The fact that Schwann cells of the PNS become reactive and express nerve growth factor (NGF) and other growth factors following axotomy suggested the possibility that peri-islet Schwann cells could become activated by islet injury. To test this hypothesis, we examined two animal models of islet injury. The first model was mice and rats injected with streptozotocin (SZ), a specific beta-cell toxin. The second model was NOD mice, a strain in which beta cells are deleted by an autoimmune process. We found that peri-islet Schwann cells became reactive following islet injury and began to express increased levels of NGF and the neurotrophin receptor p75. Lesions to the pancreas also markedly induced NGF expression by exocrine and endocrine cells. Neurotrophin expression was not unique to adult tissues since pancreatic cells transiently expressed p75, the NGF receptor Trk A, and NGF during development. These observations suggest that NGF could play an important role in pancreas during embryogenesis and in processes leading to repair following islet injury in adults.

Animals↗
PubMed1998

Endovascular stent graft repair for aneurysms on the descending thoracic aorta.

BACKGROUND: The traditional treatment of aneurysms of the descending thoracic aorta includes posterolateral thoracotomy and aortic replacement with a prosthetic graft. In this study, we report our experiences and results in endovascular stent graft placement as an alternative to surgical repair. METHODS: Between January 1989 and July 1997, a total of 68 patients (24 women) underwent replacement of the thoracic aorta. Mean age at operation was 51 years. Fifty-eight patients underwent conventional surgical treatment. All of these patients were suitable candidates for endovascular stenting; however, no stent graft material was available at the time of operation. Ten patients (1 chronic dissection, 9 atherosclerotic aneurysm) received in the past 8 months the first commercially manufactured endovascular stent graft. The mean diameter of the aneurysms in this group was 7 cm (range, 6 to 8 cm). Two stent patients were operated on using only spinal cord analgesia. All stent grafts were custom designed for each of the 10 patients. RESULTS: The 30-day mortality in the conventional group was 31% versus 10% in the stent group. Mean length of intervention was 320 minutes in the conventional group versus 150 minutes in the endovascular group. Spinal cord injury occurred in 5 patients (12%) in the surgical group, whereas none of the stented patients developed any neurologic sequelae. Mean intensive care unit stay was 13 days, followed by a mean of 10 days on a ward in the first group compared to 4 days in the intensive care unit and 6 days on the ward in the stent group. One stent was required in 2 patients, two stents were required in 3 patients, and four stents were deployed in 5 patients of our series. Five patients required transposition of the left subclavian artery to achieve a sufficient neck for the proximal placement of the stent. There was complete thrombosis of the thoracic aortic aneurysm surrounding the stent graft in 8 patients (80%). Two patients required restenting as a result of leakage (20%). Stent graft placing was performed through the femoral artery in 8 patients, whereas access was only achieved through the abdominal aorta in 2 patients. CONCLUSIONS: These preliminary results demonstrate that endovascular stent graft replacement might be a promising, cheaper, and safe alternative method in selected patients with descending thoracic aneurysms.

Adult↗
PubMed1998

Operations on the thoracic aorta and hypothermic circulatory arrest: is aprotinin safe?

INTRODUCTION: The safety of aprotinin, especially when used with profound hypothermic circulatory arrest, is still a matter of intense debate despite its presumed salutary effects on blood loss. Many investigators have reported toxic renal effects of high-dose aprotinin in such patients, but no prospective, randomized study has been conducted. To assess the potential detrimental effect of aprotinin on renal function and its putative reduction of blood loss, 50 patients undergoing thoracic aortic operations with the use of profound hypothermic circulatory arrest were randomly assigned to receive either low-dose aprotinin (1 x 10(6) kallikrein activation units) or placebo. METHODS: The specific renal tubular markers beta-2-microglobulin and beta-N-acetyl-D-glucosaminidase, as well as serum creatinine and blood urea nitrogen, creatinine clearance, sodium excretion, and potassium excretion, were measured to evaluate renal function preoperatively, immediately after the procedure, and 24 hours and 48 hours later. RESULTS: No statistically significant difference was found in any measured renal parameter between the two groups (analysis of variance). Renal dysfunction, defined as an elevation of serum creatinine early postoperatively (> or = 1.5 times the preoperative value), occurred in two patients who received aprotinin and in one patient in the control group. Temporary dialysis (hemodialysis or continuous venovenous hemofiltration) was needed in two patients in the aprotinin group versus one in the control group. Furthermore, patients treated with aprotinin had significantly less total postoperative blood loss (718 +/- 340 ml vs 920 +/- 387 ml, p = 0.04). The aprotinin recipients also had a significantly lower transfusion requirement (p < 0.05). CONCLUSION: This controlled trial of low-dose aprotinin in patients undergoing thoracic aortic operations using profound hypothermic circulatory arrest demonstrated no detectable deleterious effects on renal function; moreover, the use of aprotinin was associated with significantly lower need for transfusion.

Aged↗
PubMed1997

DNA demethylation and pericentromeric rearrangements of chromosome 1.

Rearrangements in the vicinity of the centromere of chromosome 1 are over-represented in many types of human cancer and are a characteristic feature of a rare genetic disease called ICF (immunodeficiency, centromeric heterochromatin instability, and facial anomalies). Evidence is presented that implicates DNA hypomethylation in the formation of these pericentromeric chromosomal anomalies. The DNA methylation inhibitors 5-azadeoxycytidine and 5-azacytidine, but not other tested genotoxins, induced the preferential formation of pericentromeric rearrangements of chromosome 1 at a very high frequency in a pro-B-cell line (FLEB14) and at a lower frequency in a mature B-cell line (AHH-1). These abnormal chromosomes appear identical to the diagnostic chromosomal aberrations in the ICF syndrome. A major component of the pericentromeric DNA in chromosome 1, satellite 2, was shown to be hypomethylated in an ICF B-cell line, although DNA from this cell line did not display detectable overall hypomethylation. It is hypothesized that demethylation in certain DNA regions, including in pericentromeric satellite DNA, helps lead to pericentromeric chromosomal rearrangements in lymphocytes from ICF patients and in normal lymphoblastoid cells incubated in vitro with DNA demethylating agents.

Adult↗
PubMed1997

Frequency of BCL-2/J(H) translocations in peripheral blood of follicular lymphoma patients.

Polymerase chain reaction (PCR) assays have been developed for follicular lymphoma-associated BCL-2/J(H) translocations. Few data are available on the quantitation by PCR of these translocations in peripheral blood mononuclear cells (PBM) of follicular lymphoma (FL) patients. We report that only one of five studied FL patients had a high level of these translocations in the circulation, namely, about 35,000 translocations per 5 x 10(6) PBM. This patient was stable with an excellent performance status at the time of this assay; however, he died of leukemia 1 month later.

Genes, Immunoglobulin↗
PubMed1997

[Paroxetine-induced neuroleptic malignant syndrome].

We report on a 22-year-old schizophrenic patient who attempted suicide and suffered an epidural hemorrhage. 16 days after the neurosurgical operation. After several weeks of treatment with promethazine, 1 day after intake of paroxetin he partially lost consciousness and developed extrapyramidal symptoms and vegetative disorders. Hyper-Ck-aemia up to 680 U/l was observed. Malignant neuroleptic syndrome (MNS) was diagnosed, which led to withdrawal of paroxetin and promethazine. He was put on dantamacrine and amantadine until the symptoms resolved. To date there have been few reports on MNS under tricyclic antidepressants and selective serotonin inhibitors. The influence of the central serotonergic system on the pathophysiology of MNS is discussed.

Adult↗
PubMed1997

Surgical treatment of aortic arch aneurysms in profound hypothermia and circulatory arrest.

BACKGROUND: This study was undertaken to define the factors that influence mortality rate and neurologic outcome after repair of the aortic arch and various portions of the thoracic aorta in patients with profound hypothermia and circulatory arrest. METHODS: Between November 1986 and January 1996, 105 patients were treated surgically for aortic disease involving the transverse aortic arch. Profound hypothermic circulatory arrest and selective brachiocephalic perfusion was used in all patients. In 19 patients retrograde cerebral perfusion was instituted during the period of circulatory arrest. Independent predictors for 30-day mortality and permanent neurologic deficits were evaluated by multiple logistic regression. RESULTS: Thirty-day mortality for the entire group was 19% (20/105); 21.2% for urgent versus 15.4% for elective cases, respectively. Statistical analysis showed that age is the most important factor that significantly influences mortality rate (p < 0.0145) and neurologic outcome (p < 0.006). Variables such as circulatory arrest time (p < 0.24), previous cardiac or aortic operations (p < 0.19), and sex (p < 0.55) failed to show any influence on mortality rate. Permanent neurologic deficits were diagnosed in 12.9% (11/85) of the patients. CONCLUSIONS: The incidence of permanent neurologic dysfunction as well as the mortality rate are predominantly related to the age of the patient. In this patient group, statistical analysis failed to show a direct correlation between duration of circulatory interruption and neurologic outcome.

Adolescent↗
PubMed1997

Exotic reptile bites.

Reptiles are a growing part of the exotic pet trade, and reptile bites have been considered innocuous in the emergency medicine literature. Two cases are reported of reptile bites, one from a green iguana and the other from a reticulated python. The treatment concerns associated with reptile bites are discussed.

Adult↗