Search PubMed⌕ Search

Biomedical subjects

E Alpert

Publications and source records attributed to E Alpert.

At least 19 recordsLinked to original sources
PubMed2003

Efficacy of mycophenolate mofetil combined with very low-dose cyclosporine microemulsion in long-term liver-transplant patients with renal dysfunction.

BACKGROUND: Cyclosporine (CsA)-induced renal dysfunction is common after liver transplantation. We evaluated the efficacy of tapering CsA to a very low dose and introducing mycophenolate mofetil (MMF) in long-term liver-transplant recipients with renal dysfunction. In addition, we assessed the impact of this strategy on calcineurin inhibition and on transforming growth factor (TGF)-beta levels. METHODS: We prospectively enrolled 19 adult, long-term (>1 year) liver-transplant recipients with a decreased creatinine clearance greater than 25% compared with the first month posttransplant. MMF was introduced, and CsA was tapered to 25 mg twice daily. Calcineurin inhibition and TGF-beta were measured at baseline and 3 months thereafter. RESULTS: The CsA dose was tapered over 13+/-3 weeks. At 1-year follow-up, serum creatinine decreased from 141+/-24 to 105+/-22 micromol/L (P=0.002), creatinine clearance increased from 53+/-9 to 71+/-19 ml/min (P=0.02), and glomerular filtration rate increased from 40+/-13 to 64+/-18 mL/min (P=0.002). The incidence of acute rejection was 29%. Antihypertensive medications were discontinued in 71% of the patients. Although CsA levels decreased significantly, serum TGF-beta did not differ from normal controls, and calcineurin inhibition remained stable. The incidence of gastrointestinal side-effects and leukopenia was 18% and 24%, respectively. CONCLUSION: In long-term liver-transplant recipients with renal dysfunction, the introduction of MMF followed by tapering of CsA to a very low dose resulted in a significant improvement in renal function. However, this strategy maybe associated with a risk of acute rejection. The clinical pertinence of measuring serum TGF-beta levels and calcineurin inhibition remains to be determined.

Creatinine↗
PubMed2003

Do biliary endoprostheses decrease biliary complications after liver transplantation?

AIM: Most technical complications after orthotopic liver transplantation (OLT) are related to the biliary tree. This report reviews the role of routine intraoperative placement of stents to reduce biliary complications. METHODS: We retrospectively analyzed 396 consecutive OLTs. We reviewed rates of biliary complications after hepaticojejunostomy (HJA) as well as following choledochocholedochostomy (CCA) groups: "experimental" group (routine intraoperative biliary stenting, last 10 months), "recent" control group (nonstented, previous 10 months), "historical" control group (prior to that period of time). RESULTS: All groups were matched for donor/recipient characteristics and for graft cold/warm ischemia time. The overall prevalence of biliary complications was 30.7% after CCA versus 35% after HJA. In the experimental group 21 patients had a 4.8% biliary complication rate compared to the recent control and historical groups, where biliary complication rates were 30% and 32.6%, respectively (P <.05). CONCLUSIONS: The intraoperative use of biliary stents is feasible and appears to decrease the rate of biliary complications. These results support the need for a prospective randomized trial.

Choledochostomy↗
PubMed2001

Elevation of CA-125 level is due to abdominal distension in liver transplantation candidates.

BACKGROUND: CA (cancer antigen) 125 is a serologic marker used in the monitoring of ovarian cancer. Elevated levels are also reported in cirrhosis. We evaluated the range of serum CA 125 levels seen before and after liver transplantation, and examined possible factors associated with CA 125 elevation. METHODS: We examined prospectively 57 consecutive patients with cirrhosis who underwent liver transplantation. CA 125 levels were also measured in two patients with polycystic liver disease. RESULTS: The mean serum CA 125 level before transplantation was 352+/-549 u/ml, compared with 46+/-49 u/ml after transplantation (P<0.001). Multivariate analysis identified the degree of ascites as the only significant predictive variable of preoperative CA 125 level. In five patients who underwent abdominal paracentesis, the mean ascites CA 125 level (951+/-322 u/ml) was higher than that of the serum (619+/-290 u/ml) (P<0.003). In 16 hepatectomy specimens, the grade of staining for CA 125 was 0.8+/-1.4 for the mesothelium of patients with a normal serum CA 125 level, compared with 1.5+/-1.1 in patients with elevated serum levels (P=0.37). Two patients with severe abdominal distension due to polycystic liver disease but without ascites had elevated serum CA 125 levels. DISCUSSION: CA 125 concentration is elevated in the majority of patients with cirrhosis and normalizes after liver transplantation. It is a reflection of the abdominal distention seen in these patients. Therefore, an elevation in CA 125 should not be considered a contraindication to liver transplantation in the absence of evidence of malignancy.

Ascites↗
PubMed1999

Use of older donor livers is associated with more extensive ischemic damage on intraoperative biopsies during liver transplantation.

Initial poor graft function is associated with increased morbidity and graft loss after liver transplantation. Donor age is a risk factor for the development of initial poor function. The severity of ischemic damage on intraoperative postreperfusion (0Post) allograft biopsy specimens is predictive of subsequent initial poor function. This study was performed to assess whether donor age is a risk factor for the development of ischemic damage on 0Post biopsy specimens. The records of 94 liver transplantations were reviewed. 0Post biopsy specimens were obtained after complete allograft revascularization. The severity of ischemic damage was graded as follows: 0, none; 1, minimal; 2, mild; 3, moderate; and 4, severe. Grafts were defined as older when donor age was 50 years or older. Other independent variables examined included donor cause of death, length of hospital stay, acidosis, serum alanine aminotransferase level, graft cold ischemia time, and degree of steatosis. Older grafts were associated with higher grades of ischemic damage than younger grafts (2.3 +/- 1.0 v 1.3 +/- 1.1; P =.003). Univariate and multivariate analysis identified donor age of 50 years or older as the only significant predictive variable of the severity of ischemic damage. In 16 transplantations involving older grafts, there was no statistically significant association between the severity of ischemic damage and incidence of initial poor function and graft loss. The use of older liver grafts is associated with more extensive ischemic damage immediately after graft reperfusion. Whether this early lesion identifies among older graft recipients those at risk for a worst outcome remains to be determined.

Adult↗
PubMed1999

CD44 involvement in experimental collagen-induced arthritis (CIA).

CD44 is a pro-inflammatory cell surface molecule that supports cell migration and cell lodgment in target organs. Therefore, CD44 targeting with specific monoclonal antibodies (mAbs) should be useful for the inhibition of collagen-induced arthritis (CIA) as well as other autoimmune diseases that are dependent on inflammatory cells. In the present paper, we confirm and expand previous reports showing the anti-arthritogenic effect of anti-CD44 mAbs directed against constant epitopes of the CD44 receptor. We demonstrate that such anti-CD44 mAbs can induce resistance to CIA after disease onset. Even accelerated disease developed after two injections of type II collagen was markedly inhibited by IM7.8.1 anti-CD44 mAb. Although KM81 anti-CD44 mAb is a less efficient anti-arthritogenic reagent than IM7.8.1, its Fab' fragments partially inhibit CIA. This finding implies that the antibody blocks CD44 function rather than modulating CD44 cell surface expression or mediating Fc-dependent activities. Histopathological analysis revealed that the anti-CD44 mAb markedly reduces the synovial inflammatory cellular response and the consequent damage to the joint. As CD44 is an alternatively spliced multistructural molecule, similar anti-arthritogenic effects may be achieved by mAbs directed against CD44 isoforms expressed on the pathological cells in question, but not on normal cells, thus leaving the physiological functions intact.

Animals↗
PubMed1996

Gastric toxoplasmosis in acquired immunodeficiency syndrome: antemortem diagnosis with histopathologic characterization.

Gastrointestinal symptoms attributable to Toxoplasma gondii infection are distinctly unusual, and antemortem diagnosis of gastrointestinal involvement is rarely documented, particularly in the absence of cerebral manifestations or disseminated disease. This case report describes a rare example of T. gondii infection of the stomach diagnosed antemortem in a 22-year-old Haitian woman with acquired immunodeficiency syndrome (AIDS) who presented with fever and abdominal pain. An abdominal computerized tomographic scan showed thickened gastric walls. Endoscopy showed diffusely thickened gastric folds and a fundic ulcer along the greater curvature. Light and electron-microscopic examination of gastric mucosal biopsy specimens showed active Toxoplasma infection with necrosis and intracellular trophozoites within the gastric epithelium, smooth muscle cells, macrophages, and endothelial cells. Both true cysts and pseudocysts were seen. Disseminated disease was documented by the growth of T. gondii in a tissue culture from a venous blood sample. It is concluded that some patients with AIDS, particularly those from areas endemic for Toxoplasma infection, can manifest disseminated disease in unusual locations such as the gastrointestinal tract. Documentation of active T. gondii infection based on tissue cultures of venous blood or on biopsy specimens of symptomatic extracerebral sites can lead to a rapid diagnosis of toxoplasmosis, a treatable disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Helicobacter heilmannii-like spiral bacteria in gastric mucosal biopsies. Prevalence and clinical significance.

BACKGROUND: Gastric Helicobacter pylori (Hp) is highly associated with histological gastritis and peptic ulcer disease, yet Helicobacter heilmannii (Hh, also known as Gastrospirillum hominis) may be a less frequent gastric pathogen about which less is known. PATIENTS AND METHODS: We evaluated 1223 gastric biopsies from 1042 upper endoscopies with biopsies performed over 1 year. Spiral bacteria were specifically sought in biopsies from 912 endoscopies. Clinical and pathologic data from patients with unusual spiral bacteria were tabulated and sera were evaluated for anti-Hp antibodies. RESULTS: The histologic prevalences of Hp and Hh-like bacteria were 59% and 0.5%, respectively, in 912 endoscopies. All four patients with Hh-like spiral bacteria had gastrointestinal symptoms and histologic gastritis. Two had immigrated from the Philippines and one from Belgium. Endoscopic findings and clinical course varied. One improved spontaneously; one improved following antibiotic therapy. One patient's symptoms and bacteria persisted without therapy. One patient coinfected with Hp was treated with apparent clearance of Hh but persistence of Hp. CONCLUSIONS: Helicobacter heilmannii-like bacteria can be distinguished from Hp with routine histologic stains; both bacteria are irregularly distributed. Helicobacter heilmannii appears to be a significant though uncommon cause of gastric inflammation. Some patients with Hh-like bacteria may benefit from anti-Hp therapy.

Adult↗
PubMed1995

Downregulation of phorbol 12-myristate 13-acetate-induced tumor necrosis factor-alpha and interleukin-1 beta production and gene expression in human monocytic cells by human alpha-fetoprotein.

We previously identified a specific receptor of alpha-fetoprotein (AFP) on human monocytes. Although AFP alters many immune cell functions, the effect of AFP on monocyte cytokine production is unknown. Because tumor necrosis factor--alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are important cytokines in immunoregulation, we investigated whether AFP could modulate TNF-alpha and IL-1 beta production in U937, a human monocytic cell line. Our results showed that U937 cells secreted TNF-alpha and IL-1 beta in response to either phorbyl 12-myristate 13-acetate (PMA) or IFN-gamma + LPS. In contrast, AFP significantly suppressed PMA-induced TNF-alpha and IL-1 beta production by U937 cells in a time and dose dependent fashion. Pretreatment of U937 cells with AFP resulted in maximal inhibition of PMA-stimulated TNF-alpha and IL-1 beta production by 58% and 67% respectively. AFP also inhibited interferon-gamma plus lipopolysaccharide (IFN-gamma + LPS)-induced TNF-alpha and IL-1 beta production. Furthermore, Northern blot analysis showed that AFP suppressed PMA-mediated TNF-alpha and IL-1 beta messenger RNA (mRNA) expression. PMA-induced prostaglandin E2 (PGE2) production by U937 cells was enhanced by AFP. Pretreatment with indomethacin, a cyclooxygenase inhibitor, reversed AFP-inhibited TNF-alpha production by 78%. Thus, we conclude that AFP downregulates TNF-alpha and IL-1 beta production via a PGE2-dependent mechanism.

Cell Line↗
PubMed1994

Alteration of aldolase isozymes in serum and tissues of patients with cancer and other diseases.

We studied the alteration of aldolase isozymes in the serum and tissues of patients with cancer and other diseases using radioimmunoassays specific for aldolase A, B, and C subunits. Aldolase B was predominantly found in adult liver, where aldolase A and C were distinctly low. Aldolase A and B showed almost the same concentration in fetal liver, while in neonatal liver aldolase B protein concentrations were much higher than aldolase A. In contrast, aldolase A was the predominant isozyme found in hepatoma and gastric cancer tissues, whereas aldolase B was distinctly low in hepatoma tissues, and extremely low in gastric cancer tissues. These results suggest that the aldolase A is a more fetal type of liver isozyme than the aldolase B and C, and aldolase B is a more differentiated type of liver isozyme than aldolase A and C. Serum FDP aldolase activities were elevated in half of patients with liver diseases, all patients with muscle diseases and a few patients with cancer. Serum aldolase A levels were elevated in patients with muscle diseases and cancer, but not elevated in patients with liver diseases. In contrast, serum aldolase B levels were elevated in patients with liver disease, but not elevated in patients with muscle diseases and other diseases without liver injury. Serum aldolase B levels showed a trend to decrease in cancer patients with normal GPT levels. Serum aldolase A/B ratios were significantly increased in cancer patients with normal GPT levels, whereas they showed the decreased levels in patients with liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Fructose-Bisphosphate Aldolase↗
PubMed1993

Clinical evaluation of M43: a novel cancer-associated mucin epitope.

A monoclonal antibody to colon carcinoma mucin was found to react with a colon carcinoma-associated carbohydrate epitope. This antibody was used to develop a quantitative solid phase immunoassay, M43. We prospectively and retrospectively evaluated the assay in patients with and without gastrointestinal carcinoma and compared the sensitivity and specificity with that of carcinoembryonic antigen (CEA) and CA 19-9. One hundred ninety-two patients (181 with no evidence of malignancy) referred for upper or lower gastrointestinal endoscopy were prospectively studied. Sera from 172 patients with histologically confirmed gastrointestinal adenocarcinoma were retrospectively studied. Optimal discrimination cutoffs for M43 (5 units/ml), CEA (5 ng/ml), and CA 19-9 (30 units/ml) were determined by receiver operating characteristic curves analysis. M43 was positive in 112 of 151 patients with colorectal carcinoma (sensitivity 74%) and was negative in 167 of 181 patients without carcinoma (specificity 92%). Sensitivity and specificity were 77% and 93% for CEA and 60% and 83% for CA 19-9. Sixty-four % of 73 patients with colorectal carcinoma limited to the bowel wall had a positive M43 with a mean value of 178 units/ml. Eighty-one % of 27 patients with nonhepatic metastasis had a positive M43 with a mean value of 223 units/ml. Eighty-four % of 51 patients with hepatic metastasis had a positive M43 assay with a mean value of 2532 units/ml. Sensitivity in these three groups was 67%, 82%, and 82%, respectively, for CEA and 43%, 68%, and 79%, respectively, for CA 19-9. Of 38 carcinoma patients with a negative CEA, 45% had a positive M43. No correlation between the levels of M43 and CEA in patients with colorectal carcinoma was found. We conclude that M43 is positive in most patients with colorectal carcinoma, even in early stages. As a diagnostic test, its sensitivity and specificity are equivalent to those of CEA. However, the M43 assay is measuring a tumor antigen which is fundamentally different from CEA and which is present in a high percentage of CEA-negative patients.

Adenocarcinoma↗
PubMed1992

Characterization of a lung-cancer-associated auto-antigen.

An antigen, protein X (Px), was purified from immune complexes isolated from malignant pleural effusions from patients with adenocarcinoma of the lung by EDTA treatment, PEG 8000 precipitation, protein A affinity chromatography, and Sephadex G-200 separation in the presence of 3 M NaCl. The purified antigen had a M(r) 17,000 by SDS-PAGE, and consisted of isoelectric species of pI 6.3 and 6.6. Purified Px recombined with Ig isolated from pleural fluids from patients with lung adenocarcinoma, but not with Ig from patients with breast carcinoma. Using an autologous human and heterologous chicken antibody, Px was found, by immunohistology, in the cytoplasm of some of the well-differentiated lung adenocarcinoma cells, but was not seen in normal lung or a variety of other malignant tissues. A liquid-phase competitive-inhibition RIA was developed. Over 30 ng/ml of Px were found in 9 of 15 pleural fluids from patients with lung carcinoma, none of 20 from patients with breast, ovary, stomach or colon cancer, and in 3 of 15 patients with unknown primary tumor. Our data suggest that Px may be a lung-cancer-associated autoantigen which can elicit a host humoral response in vivo.

Antigen-Antibody Complex↗
PubMed1992

Maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol levels in midtrimester trisomy 18 pregnancies.

OBJECTIVE: The purpose was to evaluate the levels of maternal serum human chorionic gonadotropin, alpha-fetoprotein, and unconjugated estriol in trisomy 18 pregnancies compared with normal singleton pregnancies. STUDY DESIGN: Sera from 14 trisomy 18 pregnancies (13 retrospectively and one prospectively ascertained) were analyzed for human chorionic gonadotropin, alpha-fetoprotein, and unconjugated estriol. RESULTS: The alpha-fetoprotein levels in the 10 trisomy 18 pregnancies without open neural tube or ventral wall defect had a median of 0.65 multiple of the median, although two had alpha-fetoprotein levels above 2.5 multiples of the median. The human chorionic gonadotropin levels had a median of 0.32 multiple of the median and the unconjugated estriol levels had a median of 0.56 multiple of the median. Although most women with trisomy 18 pregnancies had serum human chorionic gonadotropin levels that were less than 1.0 multiple of the median, three had markedly elevated human chorionic gonadotropin levels (greater than 5.0 multiples of the median). CONCLUSION: Our data are partially consistent with those previously published but suggest the possibility of a bimodal distribution of alpha-fetoprotein and human chorionic gonadotropin levels in trisomy 18-affected pregnancies, unrelated to a neural tube or abdominal wall defect. The efficiency of screening for trisomy 18 prospectively, using the three serum markers, requires further evaluation.

Adult↗
PubMed1992

Congenital deficiency of alpha-fetoprotein.

Although alpha-fetoprotein may play a role in fetal immune function or in maintenance of osmotic pressure, its exact function is unknown. We report two infants documented to have congenital deficiency of alpha-fetoprotein. One infant had cord blood levels less than 0.5 ng/ml. The second infant had a neonatal level of 120 ng/ml, which is about 2% of the usual concentration for a term newborn. These infants document the existence of congenital deficiency of serum alpha-fetoprotein. Because it is homologous to albumin, congenital deficiency of alpha-fetoprotein may be analogous to analbuminemia, a benign genetic trait.

Adult↗
PubMed1992

Alpha-fetoprotein levels in normal adults.

Alpha-fetoprotein (AFP) is a fetal specific glycoprotein normally produced primarily by the fetal liver. Normally, AFP levels decline rapidly after birth, reaching undetectable levels (less than 10 ng/ml) within several months after birth. The authors have developed a more sensitive radioimmunoassay, which has allowed them to study low levels of AFP in normal adults and to determine factors which may affect its normal level. Two hundred and seventy normal Houston blood donors were screened for the absence of hepatitis B and normal ALT levels. The mean AFP level was 3.04 ng/ml +/- 1.9 SD. There was a statistically significant higher level in men compared to women (p less than .004). Regression analysis demonstrated a statistically significant increase of AFP levels with age both in men (p less than .05) and in women (p less than .01). These data delineate the normal level of serum AFP in normal adults in the United States. With the normal level now defined, it becomes possible to compare levels in different populations including those exposed to hepatotoxins or hepatocarcinogens in the environment.

Adolescent↗