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Biomedical subjects

M M Kaplan

Publications and source records attributed to M M Kaplan.

At least 19 recordsLinked to original sources
PubMed1992

Lymphadenopathy in sclerosing cholangitis: pitfall in the diagnosis of malignant biliary obstruction.

We retrospectively reviewed abdominal computed tomographic (CT) studies from 20 patients with sclerosing cholangitis and found evidence of abdominal lymphadenopathy in 13 patients. Enlargement occurred primarily in areas draining the liver, such as the gastrohepatic ligament or celiac axis (N = 8), the porta hepatis (N = 7), and the pancreaticoduodenal region (N = 2). One patient had reactive adenopathy and retroperitoneal fibrosis. The presence of benign reactive lymphadenopathy in at least one intraabdominal location was confirmed by pathological examination of excised lymph nodes in seven patients. Malignancy was excluded by surgical exploration or clinical follow-up. We conclude that enlarged lymph nodes are a common finding by CT in patients with sclerosing cholangitis. Enlarged reactive lymph nodes in this condition should not be mistaken for evidence of periportal metastasis or cholangiocarcinoma.

Adenoma, Bile Duct↗
PubMed1992

Primary sclerosing cholangitis: refinement and validation of survival models.

The natural history of primary sclerosing cholangitis was studied in 426 patients from five medical centers. The median follow-up time was 3.0 years (range, 0.01-16.6 years); 100 patients had died by the time of last follow-up. Survival analysis (Cox proportional-hazards regression) was used to identify the variables most useful in predicting survival of patients with primary sclerosing cholangitis. Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying. A mathematical model to predict survival of patients with primary sclerosing cholangitis (based on referral values of those predictors) was statistically validated using two methods. Confidence intervals for predicting patient-specific survival probabilities are also presented. This model to predict survival could be used to stratify participants in therapeutic trials, counsel patients and their families, decide on candidacy for and timing of liver transplantation, and provide mathematical controls for evaluating the efficacy of therapies for primary sclerosing cholangitis, including transplantation.

Adult↗
PubMed1992

Monitoring thyroxine treatment during pregnancy.

Data were analyzed from 77 pregnancies in 65 hypothyroid women treated with levothyroxine (T4) to determine (a) how often, how severely, and when serum thyrotropin (TSH) and free T4 concentrations become abnormal during pregnancy in women taking constant T4 doses and (b) how much to increase T4 doses to normalize elevated serum TSH levels. Group I consisted of 36 women with previous thyroid ablation. Group II consisted of 29 women with Hashimoto's thyroiditis. Serum TSH levels rose above normal (greater than 4 microU/mL) during pregnancy more often in Group I (76%) than in Group II (47%) during treatment with constant T4 doses, and mean serum free T4 levels decreased significantly in both groups, by 47% in Group I and by 35% in Group II, compared to preconception values. Serum TSH concentrations rose above 20 microU/mL in 22% of the women, and serum free T4 concentrations fell below normal in 13%. Elevated serum TSH levels usually were detected by the first TSH test during pregnancy, as early as 4 weeks gestation. Of those women tested after an initial normal serum TSH value during pregnancy, 30% had an elevated serum TSH concentration later in the pregnancy. Of 12 women followed through two pregnancies, 10 had elevated serum TSH values in both pregnancies, 1 had normal serum TSH values in both, and 1 had discordant serum TSH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Monitoring↗
PubMed1992

Assessment of thyroid function during pregnancy.

Assessment of a woman's thyroid function often is necessary during pregnancy, since either uncorrected hypothyroidism or hyperthyroidism can adversely affect pregnancy outcome. Pregnancy-induced changes in thyroid hormone economy, particularly the major alterations in thyroid hormone binding to serum proteins, change the results of some commonly used thyroid hormone measurements. In vivo isotopic testing, including scintiscanning and thyroid radioiodine uptakes, cannot be used. Because of advances in assay technology, the best strategy for thyroid function assessment is now based on a high sensitivity serum thyroid-stimulating hormone (S-TSH) measurement as the first-line test. When S-TSH levels are high, indicating hypothyroidism, follow-up tests include serum free T4 and, if appropriate, antithyroid antibody measurements. The great majority of cases of hypothyroidism are due to Hashimoto's thyroiditis or prior thyroid ablation for hyperthyroidism or thyroid cancer. When S-TSH levels are low, suggesting hyperthyroidism, confirmatory tests are serum free T4 and free T3 measurements. Graves' disease is by far the most common cause of hyperthyroidism during pregnancy. Other causes, including those mediated by high hCG levels, can be distinguished from Graves' disease by careful clinical evaluation.

Female↗
PubMed1992

Identification of localized autoantibody epitopes in thyroid peroxidase.

Recent reports have disagreed on the nature of the autoantibody epitopes in thyroid peroxidase (TPO). We used immunoprecipitation of recombinant human TPO constructs to determine if localized autoantibody binding sites exist in this autoantigen. In vitro transcription and translation of TPO cDNA fragments yielded 35S-labeled products consisting of either full-length protein (933 amino acids) or N-terminal peptides of 631, 455, and 120 amino acids. Immunoprecipitates analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed that the Hashimoto's sera consistently precipitated the full-length and the 631 amino acid products, but not the shorter N-terminal peptides. An additional construct resulting in a full-length TPO peptide with an internal deletion of amino acids 4-455 was also made, and this product was also precipitated by the Hashimoto's sera. A fusion protein consisting of maltose binding protein followed by amino acids 456-933 of human TPO was produced in Escherichia coli and subjected to Western blot analysis using the Hashimoto's sera. The Hashimoto's sera reacted with the MalTose binding protein TPO (MBP/TPO) fusion protein, but not a control fusion protein (MBP/LacZ alpha). Together, these results indicate the presence of localized autoantibody epitopes in the portion of the human TPO molecule from amino acids 456 to 933, with at least one binding site located between amino acids 456 and 631.

Autoantibodies↗
PubMed1992

Immunoreactivity to Yersinia enterocolitica antigens in patients with autoimmune thyroid disease.

Recent reports have suggested that Yersinia enterocolitica proteins encoded by a 72-kilobase virulence plasmid (known as release proteins and now identified as YOP2-5) are antigens recognized specifically by patients with Graves' disease and of potential etiological importance in this disorder. To examine this hypothesis, we evaluated immune responses to YOP in patients with autoimmune thyroid disease and in normal controls. Humoral responses to Yersinia were assessed using Western blots of crude Y. enterocolitica membrane proteins, Yersinia release proteins (YOP2-5), and human thyrocyte membranes. Twenty-four of 25 Graves' and 10 of 18 Hashimoto's patients showed reactivity with the release proteins, primarily the 67-, 46-, 36-, and 25-kilodalton bands. However, 17 of 24 normal subjects also demonstrated serological reactivity to the release proteins, and the pattern of reactivity of these sera was similar to that in the thyroid patients. No correlation was noted between serological reactivity to the release proteins and thyroid hormone levels. Patients and controls with serological reactivity to YOP also showed reactivity with Yersinia membranes. In addition to the serological studies, cellular immune responses were determined by peripheral blood mononuclear cell proliferation assays. Cellular reactivity to the release proteins was present in four of five Graves' and both Hashimoto's patients tested, but also in two of six nonthyroid illness patients with serological immunity to the release proteins. Intrathyroidal lymphocytes obtained from two Graves' patients demonstrated marked proliferation in response to the release proteins. These results indicate that there is no unique pattern of serological reactivity against Yersinia membranes or the release proteins in patients with autoimmune thyroid diseases and suggest that any causal relationship between Yersinia infection and Graves' disease may be related to T-cell immunity.

Antibodies, Bacterial↗
PubMed1992

High-sensitivity serum calcitonin assays applied to screening for thyroid C-cell disease in multiple endocrine neoplasia type 2A.

UNLABELLED: Two serum calcitonin assays with sensitivities < or = 10 pg/mL were compared to our standard radioimmunoassay (sensitivity 100 pg/mL) in multiple endocrine neoplasia type 2A (MEN 2A) screening. Values from the Nichols displacement radioimmunoassay averaged 38% higher than values from the CIS immunoradiometric assay; values from both were highly correlated, r = 0.845. In three individuals, both of the newer assays revealed abnormalities in pentagastrin tests three to four years before abnormalities were detected by the standard assay. Pentagastrin tests after total thyroidectomy were assayed by the newer methods in patients with medullary thyroid carcinoma (MTC) diagnosed at initial testing (group I); in patients with early MTC diagnosed by prospective screening (group II); and in patients with pure C-cell hyperplasia detected by prospective screening (group III). At least 64% of group I, at least 25% of group II, but none of group III had detectable postoperative C-cell function. CONCLUSIONS: 1) The previous estimate of 12 years as median age of onset of C-cell disease in MEN 2A is probably three to four years too old. 2) Patients diagnosed with early MTC by screening had not necessarily skipped a preneoplastic phase of C-cell hyperplasias. At least some early disease was not detected by the standard assay. Higher sensitivity assay should improve screening for C-cell disease by earlier disease detection. 3) Biochemical cure by thyroidectomy after the development of MTC is not as frequent as previously thought, but the apparent cure rate of pure C-cell hyperplasia remains 100%.

Adolescent↗
PubMed1992

Serum interleukin-2 and tumor necrosis factor-alpha in primary biliary cirrhosis: decrease by colchicine and relationship to HLA-DR4.

Colchicine improves liver function tests and survival in primary biliary cirrhosis (PBC); however, its mechanism of action in PBC is unknown. Because elevated interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF) have been found in various inflammatory diseases, we measured serum levels of IL-2 and TNF in 28 PBC patients before and during treatment with either colchicine or placebo. Compared with normal controls, untreated PBC patients had increased serum IL-2 (39 +/- 13 U/ml vs. 0.8 +/- 0.5) and TNF (549 +/- 162 pg/ml vs. nondetectable). During colchicine treatment, both IL-2 and TNF levels decreased significantly (57 +/- 24 to 40 +/- 22, p less than 0.04; 586 +/- 295 to 445 +/- 295, p less than 0.02). No significant changes in IL-2 or TNF levels occurred in the placebo-treated patients. DR4-positive patients had elevated levels of IL-2 at entry, compared with DR4-negative patients (67 +/- 26 vs. 14 +/- 5, p less than 0.04). The effect of colchicine in PBC may be due, in part, to modulation of IL-2 and TNF levels. Alternatively, the changes in IL-2 and TNF may simply reflect the overall improvement in biochemical tests of liver function related to colchicine therapy. DR4 appears to relate to serum levels of these cytokines in PBC and, possibly, also to the response to colchicine.

Biological Assay↗
PubMed1991

Treatment of primary biliary cirrhosis with low-dose weekly methotrexate.

Nine women with symptomatic precirrhotic primary biliary cirrhosis have been treated with oral pulse methotrexate, 15 mg/wk, for 12-34 months. Three women had pruritus, two fatigue, and four pruritus and fatigue. Itching disappeared and fatigue lessened or disappeared in all within 4-11 months after starting methotrexate. All who itched were able to discontinue cholestyramine (five) or antihistamines (two). Biochemical tests of liver function improved in all patients and then worsened in three when methotrexate was discontinued or the dose lowered. Mean serum alkaline phosphatase decreased from 471 to 171 U/L (P less than 0.01), serum bilirubin from 0.99 to 0.59 mg/dL (P less than 0.05), and serum alanine aminotransferase from 132 to 61 U/L (P = 0.02), and serum cholesterol fell from 265 to 213 mg/dL (NS). The decrease in serum cholesterol was significant, P = 0.05, if data were used just from the six women whose baseline serum cholesterol levels were elevated. Serum albumin remained normal in all. The serum bilirubin levels became normal in three of four patients with elevated levels. The serum alkaline phosphatase levels became normal in four patients and the alanine aminotransferase levels in three. Liver histology improved in five patients and was stable in the remaining four based on a quantitative evaluation of coded liver biopsy specimens. The improvement in histology was primarily due to decreased portal inflammation and bile duct injury. The titer of antimitochondrial antibody decreased in seven patients. The data suggest that methotrexate may be effective treatment for precirrhotic primary biliary cirrhosis. Controlled trials are needed to evaluate long-term efficacy and toxicity.

Adult↗
PubMed1991

Historical perspective of the origins and development of international veterinary public health in the World Health Organisation.

The World Health Organisation (WHO) worked vigorously to implement and develop veterinary public health (VPH) activities during the first twenty years of its existence. These activities have continued and expanded into new fields in subsequent years, and will no doubt continue. The initial challenge was to establish the importance and usefulness of the veterinary profession to human medical and public health problems. Collaborative actions and coordinated research on the major zoonoses, food hygiene and comparative medicine helped to achieve this result along with programmes applying this knowledge in member nations, and particularly developing countries which comprise the vast majority of world population. The VPH discipline must now take into account and adapt its effort to the ever-changing social and economic conditions affecting human health. The veterinary profession can help to improve human health, and VPH structures offer an effective channel for doing so.

Animals↗
PubMed1991

Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism.

We studied a large population (n = 2575) of unselected ambulatory persons older than 60 years to determine the prevalence of a low serum thyroid-stimulating hormone (TSH) level, ie, of less than 0.1 mU/L using a sensitive assay, a level suggestive of hyperthyroidism in younger adults. One hundred one persons (3.9%) had a low serum TSH level. About half of them (51/101) were taking thyroid hormone. Of the remainder, 44 were not hyperthyroid did not become so during up to 4 years of follow-up. Forty-one of the 44 euthyroid persons had a serum thyroxine level of less than 129 nmol/L; repeated testing showed a serum TSH level of more than 0.1 mU/L in the three euthyroid persons with a serum thyroxine level of more than 129 nmol/L. Only six were hyperthyroid or became so during the follow-up period; all had a serum thyroxine level of more than 129 nmol/L. Routine clinical examination was not a sensitive indicator of hyperthyroidism and did not permit discrimination from euthyroidism. A low value of serum TSH alone, while it had high sensitivity and specificity for hyperthyroidism, had a low positive predictive value (12%) for this diagnosis; addition of the thyroxine assay raised the predictive value fivefold to 67%. A low value of serum TSH is far more common in older persons than is hyperthyroidism. Low values in euthyroid persons are accompanied by a clearly normal serum T4 concentration (less than 129 nmol/L) or by a serum TSH level of more than 0.1 mU/L on repeated testing. We recommend measurement of the serum TSH thyroid concentration, using a sensitive assay, as the initial step in testing any older person for possible hyperthyroidism. Measurement of the serum T4 concentration or the free T4 index on the same sample would be needed only in the approximately 2% with a serum TSH level of less than 0.1 mU/L; alternatively, the TSH assay in these could be repeated at a later time.

Aged↗
PubMed1991

Treatment of primary sclerosing cholangitis with oral methotrexate.

Ten patients with well-documented primary sclerosing cholangitis who had no signs of portal hypertension or liver failure were treated with oral pulse methotrexate for at least 1 yr. The methotrexate dose averaged 15 mg/wk (0.2 mg/kg/wk). All six patients who were symptomatic became asymptomatic within 1-5 months of starting methotrexate. Biochemical tests of liver function improved in all patients. The alkaline phosphatase value decreased from a mean (+/-SD) of 373 +/- 210 IU to 140 +/- 77 IU (p = 0.0008), the mean alanine aminotransferase (ALT) from 115 +/- 74 to 76 +/- 79 U/L (p = 0.005), and the mean aspartate aminotransferase (AST) value from 88 +/- 37 to 57 +/- 40 U/L (p = 0.007). The improvement in mean bilirubin (1.19 +/- 1.41 to 0.67 +/- 0.25 mg/dl) was not statistically significant. Serum albumin remained normal (3.97 +/- 0.46 to 4.22 +/- 0.36 g/dl). Nine patients had a repeat liver biopsy after 1 yr of methotrexate therapy. Six of the nine showed histologic improvement with a reduction in inflammation. The other three liver biopsies were unchanged. Repeat cholangiograms were done in six patients. Two showed improvement. In one of the two, who had early disease, the cholangiogram became normal, and the liver biopsy was markedly improved. The other four cholangiograms showed no progression of disease. No toxicity was detected in these 10 patients. These results suggest that low-dose oral methotrexate therapy is effective in primary sclerosing cholangitis if treatment is begun before signs of portal hypertension or liver failure occur.

Administration, Oral↗