Refractory sclerotherapy-induced esophageal strictures.
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Biomedical subjects
Publications and source records attributed to E Alpert.
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An 18-year-old student sustained a basilar skull fracture and seventh cranial nerve paralysis from a car-pedestrian accident. In the emergency room she scored 12 on the Glasgow Coma Scale. Dexamethasone 16 mg/day was administered in an attempt to reverse the facial palsy. After a 14-day course of therapy, the corticosteroid was abruptly withdrawn over a 24-hour period. On the day the dexamethasone was discontinued, the patient became severely depressed and developed an organic psychosis that persisted for ten weeks, necessitating psychiatric hospitalization. Psychopharmacologic therapy was required to control her mental symptoms. After discharge from the psychiatric hospitalization, she participated in a cognitive retraining program for closed head injury patients and soon thereafter returned to her studies. A possible explanation for this patient's organic psychosis was the abrupt withdrawal of steroid therapy. Alternate etiologies include the closed head injury and reactive psychosis. Comparison of this patient's symptoms with other cases of steroid psychosis showed similarities in time of onset, presentation of symptoms, and duration of psychosis. The use of steroids in closed head injury patients for the reduction of cerebral edema, is an important indication; however, adverse reactions such as psychoses can be prevented by slow withdrawal of the drug. Psychiatrists should be aware of the possibility of withdrawal psychoses as a result of steroid therapy in closed head injury patients.
Maternal serum alpha-fetoprotein (MSAFP) screening was offered in a private suburban practice to 21,000 nondiabetic and 442 diabetic women with apparently normal pregnancies. Using 2.5 or greater multiples of the median as the normal upper limit, 249 (1.2%) had a raised MSAFP level. There were 25 neural tube defects (NTDs) (1.2/1,000 births); 18 were detected by screening and two by ultrasound scanning. Three had closed spina bifida lesions. Two had anencephaly with normal MSAFP levels, but were studied at more than 24 weeks' gestation. An additional 13 with raised MSAFP levels had other congenital defects. One in 400 women screened had a recommended amniocentesis; 26.4% of them had a fetus with an NTD or major malformation. Our detection efficiency before 24 weeks' gestation for anencephaly was 85.7% (12/14), 62.5% (5/8) for open and closed spina bifida, and 1/1 for encephalocele. A raised MSAFP level occurred in ten (2.3%) of the 442 diabetic women, four (0.9%) of whom had a fetus with an open NTS. A screening program should be established only where there is linked excellent interdisciplinary support among obstetrician, laboratory, clinical geneticist, ultrasonographer, and an identified program coordinator.
The human serum albumin gene was analyzed by restriction endonuclease mapping of chromosomal DNA isolated from a patient with congenital analbuminemia. Following digestion with a variety of restriction endonucleases, the DNA from this individual produced the same fragments with homology to a serum albumin cDNA probe as did a control DNA specimen. Therefore, the genetic condition of congenital analbuminemia is not caused by any gross structural rearrangement or deletion of the gene itself, but may result from an abnormality in the gene's fine structure, perhaps affecting regulation or processing of the primary RNA transcript.
A radioimmunoassay specific for human aldolase A subunits was used to measure human aldolase A (ALD-A) in human serum. The double antibody competitive inhibition radioimmunoassay technique used radioiodinated purified ALD-A as ligand, chicken antisera specific for human ALD-A and rabbit antichicken IgG. The serum levels of ALD-A in 42 normal healthy subjects ranged from 130 to 210 ng/ml (mean average, 171 +/- 39 ng/ml). In 177 hospitalized patients without cancer, muscle diseases, or hemolytic anemia, the ALD-A serum levels ranged from 125 to 220 ng/ml. In contrast, 82% of 260 patients with various types of malignancy had ALD-A serum concentrations above the normal range. The CEA levels increased only 44% of the sera of 80 patients with cancer of the digestive tract, whereas the ALD-A levels were increased in 86% of the patients. The AFP levels were greater than 100 ng/ml in only 70% of the sera of 33 liver cell carcinoma patients, whereas the ALD-A levels were increased in 94% of these sera. The measurement of serum ALD-A by radioimmunoassay may be a valuable adjunct in the clinical diagnosis of certain cancer patients.
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Radioimmunoassays specific for fructose-1, 6-diphosphate aldolase isozymes were developed for the quantification of human aldolase A, B and C. The method is a double-antibody radioimmunoassay using radioiodinated purified aldolase A, B and C as ligand, chicken antibodies to aldolase A, B and C, and rabbit antibodies to chicken IgG. The Iodogen method was used for the iodination of aldolase A, B and C in this study. Aldolase A was predominantly high in concentration in muscle, aldolase B was high in normal adult liver, and aldolase C was high in adult brain. Aldolase A was elevated in hepatoma tissue and hepatoma cell lines, where aldolase B was distinctly low. Normal serum levels for the three isozymes were determined. The aldolase A levels in serum obtained from 41 normal subjects were 170 +/- 39 ng/ml. Serum aldolase A levels were increased in many patients with cancer and muscle diseases, but were not increased in patients with hepatitis or other benign diseases. Serum aldolase B levels obtained from 11 normal subjects were 28.5 +/- 9.2 ng/ml. Serum aldolase B levels were increased in patients with hepatitis and correlated well with serum GPT levels. Serum aldolase C levels obtained from 12 normal subjects were 2.4 +/- 0.7 ng/ml. The determination of aldolase A, B and C by radioimmunoassay may be a valuable tool in biochemical and clinical studies of aldolase isozymes.
A radioimmunoassay specific for human aldolase A was used to measure human aldolase A levels in human tissue and serum of patients with various liver diseases. The method was a double-antibody technique using radio-iodinated purified aldolase A, chicken antibody to aldolase A, and rabbit antibody to chicken immunoglobulin G. Normal liver tissue contains only a small amount of aldolase A. In contrast, aldolase A predominates in liver cell carcinoma tissue. Aldolase A levels in the sera of normal subjects were 171 +/- 39 ng/ml (mean +/- 2 SD). In almost all of the nonmalignant liver diseases, the aldolase A levels remained less than 210 ng/ml. The serum aldolase A levels increased remarkable only in fulminant hepatitis. in contrast, 32 of 34 patients with liver cell carcinoma and all of 29 patients with metastatic liver carcinoma showed clearly increased serum aldolase A levels. More patients with primary liver cell carcinoma had increased serum aldolase A levels than elevations of serum alpha-fetoprotein. These results suggest that the determination of aldolase A by radioimmunoassay may be useful to differentiate malignant form nonmalignant liver diseases.
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Radioimmunoassays specific for ALD isozymes were developed for the quantification of human ALD-A, -B, and -C. The method is a double antibody radioimmunoassay consisting of purified radioiodinated ALD-A, -B, and C as ligand, chicken antibodies to ALD-A, -B, and -C, and rabbit antibodies to chicken IgG. The Iodogen method was used for the iodination of the purified isozymes. ALD-A was present in high concentration in muscle, ALD-B in adult liver, and ALD-C in adult brain. ALD-A was elevated in hepatoma tissue and hepatoma cell lines, whereas ALD-B was distinctly low. Normal serum levels for the three isozymes were determined. The ALD-A level in the serum from 41 normal subjects was 170 +/- 39 ng/ml. Serum ALD-A level was increased in many patients with cancer and muscle diseases, but not in patients with hepatitis or other benign diseases. Serum ALD-B level in 11 normal subjects was 28.5 +/- 9.2 ng/ml. Serum ALD-C level in 12 normal subjects was 2.4 +/- 0.7 ng/ml. The determination of ALD-A, -B, and -C by radioimmunoassay may be a valuable tool in biochemical and clinical studies of these isozymes.
A radioimmunoassay was developed for the direct quantification of aldolase B in human serum and tissues. The method is a double antibody radioimmunoassay technique using radioiodinated aldolase B homopolymer as ligand, chicken antibodies to aldolase B and rabbit antibodies to chicken IgG. This radioimmunoassay was shown to be specific for the aldolase B subunit, with no cross-reactivity with either human aldolase A subunit or homopolymeric human aldolase C (C4). The lowest measurable amount by this method was 2 ng/ml. Aldolase B is predominantly found in normal liver tissue, with relatively high aldolase B levels also observed in kidney. Aldolase B levels in the serum obtained from 11 normal subjects ranged from 23 to 38 ng/ml, with a mean of 28.5 +/- 9.2 (S.D.) ng/ml. Almost all of patients with hepatitis had serum aldolase B levels greater than 30 ng/ml. In cancer patients, serum aldolase B was slightly elevated in patients with metastatic liver cancer and primary lever cell carcinoma, whereas no elevation of serum aldolase B was shown in patients without liver metastasis.
Although bougienage is widely used to treat benign esophageal stricture, the rate of stricture recurrence and the long-term effectiveness of bougienage are unknown. We studied the natural history of esophageal stricture in 154 patients in whom bougienage was used as primary therapy. Dilatations were considered successful in terms of relief or major improvement of dysphagia in 84.5% of 103 patients followed 6 mo or longer (median, 26 mo). The risk of requiring esophageal dilatation after the initial episode was greatest in the first year of follow-up; thereafter, a smaller fraction of patients required dilatation each year. Forty-three percent of patients required no further dilatations, and a life-table analysis showed that 36% of patients would require no further dilatation during a projected 4-yr follow-up. The median frequency of subsequent dilatation was less than once a year. We were unable to identify any significant factors, such as initial severity of stricture, cause of stricture, presence of active esophagitis, or initial caliber of dilatation, that could predict the need for subsequent dilatation. Our results suggest that patients with benign strictures fall into two groups. In one group, the natural history was to improve or become asymptomatic after an initial series of dilatations, and only a small proportion eventually developed recurrent symptoms. The second group (46% of patients) required further dilatations to treat dysphagia during the first year of follow-up. Two-thirds of these patients needed regular dilatations in subsequent years. We conclude that bougienage is effective treatment for benign esophageal strictures, and should be utilized as primary therapy for most strictures.
A solid-phase, non-competitive radioimmunoassay for aldolase A in human serum has been developed. Human aldolase A was purified from muscle, and specific antisera to the purified aldolase A were obtained from chickens. Specific IgG anti-human aldolase A was purified by affinity chromatography. Disposable polypropylene plates were coated with specific IgG antibody and used for radioimmunoassay with 125I-specific IgG antibody to aldolase A. The non-specific binding was minimized by saturating the binding sites of the plates with 2% ovalbumin in 0.1% Tween 20. This radioimmunoassay is specific for the aldolase A subunit, with no cross-reactivity with human aldolase B subunit or homopolymeric human aldolase C(C4). The serum aldolase A immunoreactivities of 33 normal subjects ranged from 124 to 212 ng/ml with a mean of 178 +/- 41 ng/ml (+/- 2 SD). Ninety-three patients' sera were assayed with both a solid-phase non-competitive radioimmunoassay and a competitive double antibody radioimmunoassay developed in our laboratory and the results showed a high degree of correlation (r = 0.912; p less than 0.001). Rapidity and simplicity of the solid-phase assay makes it superior to other methods for the measurement of serum aldolase isozymes.
Maternal serum alpha-fetoprotein (AFP) screening of routine pregnancy is a valuable tool for the prenatal detection of neural tube defects (NTDs). Against our background experience with greater than 24,000 screened pregnancies, we have studied 411 pregnant insulin-dependent diabetic women. More than a tenfold increase (19.5/1,000) in the frequency of NTDs was observed in the offspring of these diabetic patients (p less than 0.000001). Serum AFP values were lower in diabetic than in nondiabetic women. Our data indicate that the normal standard of care for diabetic pregnancy should include serum AFP screening.
We evaluated D-penicillamine in the treatment of primary biliary cirrhosis. In a prospective double-blind trial, 26 patients received D-penicillamine (250 mg four times a day), and 26 received an identical placebo. Although the desired urinary excretion of copper was achieved in patients taking D-penicillamine, there was no improvement in survival or symptoms after 28 months. Serum bilirubin and alkaline phosphatase increased equally in both groups. Alanine and aspartate aminotransferases were lower in the D-penicillamine group, but serum albumin was also lower in this group. Liver histology worsened equally in both groups. Major side effects, some appearing more than 24 months after the start of treatment, occurred in 31 per cent of the patients receiving D-penicillamine. Less serious side effects occurred in an additional 46 per cent. We conclude that D-penicillamine at the dosage we used is not effective in the treatment of primary biliary cirrhosis and is associated with a high incidence of serious side effects.
Lysyl oxidase and collagenase activities were measured in experimental acute and chronic liver injury in mice and rats, and correlated with collagen synthesis and accumulation. Acute liver injury was induced in mice and rats by a single dose of carbon tetrachloride given by gavage, and also in mice by a single injection of murine hepatitis virus. Chronic liver injury was induced in rats by repeated injections of carbon tetrachloride. Elevated plasma glutamic oxaloacetic transaminase levels, increased hepatic prolyl hydroxylase activity, and increased synthesis of collagen-bound hepatic hydroxyproline occurred in animals with acute as well as with chronic liver injury. However, only chronic liver injury appeared to be associated with fibrosis, increased collagen-bound hydroxyproline content, increased hepatic lysyl oxidase and collagenase activities, as well as with increased serum lysyl oxidase activity. These data suggest that lysyl oxidase and collagenase may play an important role in the collagen accumulation associated with hepatic fibrosis.
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A radioimmunoassay was developed for the direct quantification of aldolase A in human serum. The method is a double antibody radioimmunoassay using radioiodinated aldolase A4 homopolymer as ligand, chicken antibodies to aldolase A, and rabbit antibodies to chicken IgG. The lowest measurable amount by this method was 2 ng (0.01 U). The radioimmunoassay was shown to be specific for the aldolase A subunit, with no cross-reactivity with human aldolase B subunits or homopolymeric human aldolase C (C4). The immunoreactive aldolase A in the sera of 41 normal healthy subjects ranged from 130 to 210 ng/ml (0.81-1.31 U/1), with a mean of 171 /+- 39 ng/ml.