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Biomedical subjects

M Kaplan

Publications and source records attributed to M Kaplan.

At least 145 records · Page 8Linked to original sources

Advances in the management of patients with thyroid disease.

Discoveries related to thyroid immunology, especially concerning the thyroid-stimulating hormone (TSH) receptor, may facilitate new immunologic approaches to the therapy of Graves' disease and the thyroiditis syndromes. Advances in genetics are being applied to the thyroid hormone resistance syndromes and papillary and medullary carcinomas. The development of ever more sensitive TSH assays has led to the detection of subclinical thyroid disease, which has special implications for the sick and elderly patients. Sensitive TSH assays also allow more precise titration of levothyroxine (T4) dosages, especially for patients with a past history of thyroid cancer. Evidence continues to accumulate suggesting that postmenopausal women on T4 doses that suppress the TSH level below 0.1 ulU/mL have lower bone mineral density than matched patients with healthy TSH levels. Also, pregnant hypothyroid women need higher T4 doses to normalize the TSH levels. In the evaluation of thyroid nodules, fine-needle aspiration biopsy is the single most definitive modality in selecting the patients for surgery. Scintigraphy provides a complimentary role, especially in defining autonomously functioning thyroid adenomas (AFTA), because these should not be treated with T4 suppression. Ultrasound-guided needle biopsy is occasionally helpful with nodules that are difficult to palpate. Concern for possible tracheal compression after treatment of toxic multinodular goiter with large doses of radioactive iodine (I-131) in the range of 50 to 150 mCi (1.85 to 5.5 GBq) does not seem warranted. Work, primarily out of Italy, suggests AFTA can be ablated with repeat ethanol injections. Residual tissues after thyroidectomy for differentiated carcinoma can be "stunned" by tracer doses of 131I greater than 3.0 mCi (111 MBq), which diminishes the uptake and effectiveness of a subsequent therapy dose. Positron emission tomograph, imaging with thallium-201, and Technetium 99m Sestamibi can identify a small number of patients shown to have metastases from differentiated thyroid carcinoma by increasing thyroglobulin levels in the absence of 131I uptake. Several groups have recently advocated treating such patients empirically with 131I.

Adult↗

Antacid bezoar in a premature infant.

A premature infant with severe enteroviral infection was treated with Maalox for gastric bleeding. Bezoars formed, which were shown to contain high concentrations of magnesium. An association between antacid administration and bezoar formation in neonates has been previously suggested but has not until now been clearly documented.

Aluminum Hydroxide↗

Primary gastric T-cell lymphoma with cutaneous involvement. A case report and review of the literature.

Primary gastric T-cell lymphomas are extremely rare. We report a Ki-1 negative primary gastric T-cell lymphoma of the anaplastic large cell type associated with extensive involvement of the skin, gastrointestinal tract, and other organ involvement in a patient not known to be immunocompromized. Biopsy of the stomach and distal esophagus showed infiltration of gastric mucosa and the squamous epithelium by nests of large atypical cells with vacuolated or clear cytoplasm, consistent with large cell lymphoma. Immunohistochemical staining of these specimens revealed neoplastic cells bearing LCA (CD45) and T-cell markers (UCHL1/CD45R0 and CD3). This represents the only case so far with synchronous presentation of gastric, esophageal, and cutaneous involvement without evidence of regional lymph node involvement. There was no association with HTLV-1 or HIV infection. The patient had a fulminant course and a poor response to chemotherapy.

Aged↗

Autoantibody profile of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease of unknown etiology. It has been suggested that genetic and immunological factors are important in its pathogenesis. The present study examined the prevalence of 23 different autoantibodies in 25 PSC sera, by ELISA, in order to better define the autoimmune profile of PSC. The results indicate that 88% of PSC patients produced at least 1 autoantibody, and 36% had reactivity to multiple autoantibodies. Moreover, 35% of the PSC patients produced anti-endothelial-cell antibodies (AECA) and 75% of the sera contained perinuclear antineutrophil cytoplasmic antibodies (pANCA), detected by indirect immunofluorescence. The prominent ANCA autoantibody was anti-cathepsin-G, demonstrated in 35% of the patients. The multiplicity of the autoantibody profile, revealed in the present study, points to the autoimmune characteristics of PSC. In addition, the association of ANCA and of AECA in PSC may suggest a pathogenic role for these antibodies in PSC.

Antibodies, Antineutrophil Cytoplasmic↗

Oxygen saturation during and after feeding in healthy term infants.

In instrumented infants, 'normal' feeding occasionally causes respiratory changes, however, the extent of 'acceptable' oxygen desaturation is undocumented. We studied O2 saturation in healthy full-term neonates under totally natural feeding conditions unencumbered by any mechanical devices. Infants' O2 saturation was monitored continuously for 10 min of nutritive sucking and for 5 min after feeding. Twenty-one infants were studied, including 11 breast- and 10 bottle-fed infants. The distribution of saturation measurements was calculated and compared during feed vs. postfeed periods for both groups of infants. None of the infants had decreased saturation with feeding when compared to the prefeeding baseline. However, most of the infants in both groups did experience significantly lower O2 saturations after than during feeding (18 and 29% of the postfeed readings were < 90% in breast- and bottle-fed infants). Mean O2 saturations dropped from 96 +/- 2% (during feed) to 93 +/- 2% (postfeed) in breast-fed and from 95 +/- 2% (during feed) to 92 +/- 4% (postfeed) in bottle-fed infants. These findings elucidate the physiology of normal infant feeding and should be taken into account when monitoring term infants with oxygen saturation.

Blood Gas Monitoring, Transcutaneous↗

Psychiatrists' and non-physician psychotherapists' beliefs about gender-appropriate behavior: a comparison.

We adapted the Bem Sex-Role Inventory to survey therapists' beliefs about gender-appropriate behavior for hypothetical patients. We previously studied psychiatrists, finding that women were more likely to choose masculine or androgynous (high masculine and high feminine) traits as optimal for female patients while men were more likely to choose the undifferentiated (low masculine and low feminine) category for patients of either sex. In this study we used the same measure to compare psychologists and social workers to the psychiatrists, to determine the effect of medical education on these attitudes. We found that regardless of educational background, women were more likely to choose the androgynous category and men were more likely to choose the undifferentiated category. Women psychiatrists were more likely to choose masculine traits as optimal than were women non-physician therapists. Male therapists of all backgrounds were least likely to choose masculine traits as optimal for either male or female patients. Medical education per se does not seem to determine attitudes about gender-appropriate behavior. Men entering professions in which they are concerned about others' emotional well-being may have less stereotypically masculine beliefs about gender-appropriate behavior than women entering the same fields. Possible reasons for this difference are discussed.

Adult↗

Abnormal expression of the E2 component of the pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before major histocompatibility complex class II and BB1/B7 expression.

Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized histologically by nonsuppurative destructive cholangitis. Sera from patients with PBC react with a series of intramitochondrial enzymes with the immunodominant response directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Recently, using tissue sections of late-stage PBC, we showed that there is increased expression in biliary epithelial cells of patients with PDC-E2 or a molecule cross-reactive with PDC-E2. Previous work has shown that biliary epithelial cells of patients with PBC express an increased amount of class II. To address the sequence of events in the evolution of PBC, we have focused our attention in this study on early biliary epithelial lesions. In particular, we have studied the liver of 22 female patients with PBC that was diagnosed as either stage I or stage II using both a mouse monoclonal antibody that has reactivity similar to human autoantibodies as well as a human Fab combinatorial prepared from the lymph node of a PBC patient. Tissues were simultaneously stained using antibodies to PDC-E2, class II, and BB1/B7. As a positive control, tissues from late-stage PBC were studied concurrently. By determining the order of expression among the three molecules, PDC-E2, class II, and BB1/B7, we report that the expression of PDC-E2 or a PDC-E2-like molecule on biliary duct epithelium of patients with PBC precedes the expression of BB1/B7 and major histocompatibility complex (MHC) class II molecules. The alteration of an autoantigen in biliary duct epithelium may be the earliest lesion in PBC.

Adult↗

Continuous versus multiple rapid infusions of indomethacin: effects on cerebral blood flow velocity.

OBJECTIVE: Therapeutic administration of indomethacin for patent ductus arteriosus (PDA) closure has been documented to decrease cerebral blood flow velocity which may be harmful to the vulnerable premature neonate. We have therefore compared the effects of administering indomethacin by rapid injection versus slow, continuous indomethacin infusion at the same total therapeutic dose on middle cerebral artery (MCA) systolic and diastolic flow velocity, resistance index, and cerebral blood flow (as reflected by the integrated area under the curve). METHODS: Premature neonates (< 1750 g) documented echocardiographically to have a PDA were randomized to receive indomethacin either by three rapid injection doses or by continuous intravenous infusion over the ensuing 36 hours, providing an equivalent total dose. Echocardiograms and transcranial color flow mapping of the MCA flow velocity were measured at baseline and serially following initiation of therapy in both groups. Effects on cerebral blood flow velocity are presented. RESULTS: Eighteen infants [rapid injection-1.2 +/- 0.3 kg (n = 9) and continuous-1.1 +/- 0.2 kg (n = 9)] were studied. In the rapid injection treated infants decreased flow velocity in the MCA as manifested by abrupt, significant decreases in systolic (to 70 +/- 8% baseline) and diastolic (to 65 +/- 13% baseline) flow velocity and area under the curve (to 60 +/- 10% of baseline) were evident by 4 minutes and progressed to 30 minutes after treatment initiation. These changes were not observed in the group treated with continuous indomethacin. Both therapeutic modalities were equally successful in closing the ductus, although the numbers are too small to definitively determine therapeutic efficacy. CONCLUSIONS: Slow, continuous infusion eliminated the decrease in cerebral flow velocity and appears to be effective in closing the PDA.

Blood Flow Velocity↗

Apolipoprotein E (ApoE), a novel heparin-binding protein inhibits the development of Kaposi's sarcoma-like lesions in BALB/c nu/nu mice.

Recombinant apolipoprotein E-3 (ApoE-3), expressed in Escherichia coli, was purified and used in an in vitro and an in vivo model system for acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS). This protein blocked cell proliferation and chemotaxis of AIDS-KS cells in response to activated lymphocyte conditioned medium (AL-CM) and oncostatin M (OSM). ApoE-3 also inhibited the formation of neoangiogenic lesions induced in BALB/c nu/nu mice by AIDS-KS cells. These findings represent a novel and potentially less toxic therapeutic approach for the treatment of AIDS-KS.

Acquired Immunodeficiency Syndrome↗

Identification and culture of Kaposi's sarcoma-like spindle cells from the peripheral blood of human immunodeficiency virus-1-infected individuals and normal controls.

We examined 26 patients with human immunodeficiency virus-1 (HIV-1)-associated Kaposi's sarcoma (KS), and 76 HIV-1-infected (HIV-1+) people without KS or uninfected (HIV-1-) controls for the presence of circulating KS-like spindle cells. Adherent cells that had spindle morphology and several characteristics of spindle cells of KS lesions (KS cells) were identified in the peripheral blood mononuclear cell fraction only after culture in the presence of conditioned medium (CM) from activated lymphocytes. The peripheral blood-derived spindle cells (PBsc) expressed a variety of endothelial cell markers, such as Ulex europaeus I lectin, EN4, EN2/3, EN7/44, CD13, CD34, CD36, CD54, ELAM-1, and HLA-DR. However, they were negative for CD2, CD19, PaIE, and factor VIII-related antigen. The PBsc produced angiogenic factors as evidenced by the ability of CM from these cells to promote growth of normal vascular endothelial cells. In addition, subcutaneously injected PBsc stimulated angiogenesis in vivo in athymic nude mice. We determined that the number of PBsc grown from the peripheral blood of HIV-1+ patients with KS or at high risk to develop KS were increased by 78-fold (P = .0001) and 18-fold (P = .005), respectively, when compared with HIV-1- controls. The number of spindle cells cultured from the HIV-1+ patients at low risk for developing KS, eg, HIV-1+ injection drug users, showed no statistical increase when compared with HIV-1- controls. The presence of increased PBsc with characteristics of KS cells in HIV-1+ KS patients or patients at high risk for developing KS gives insights into the origin of KS cells and may explain the multifocal nature of the disease. In addition, this may be useful in predicting the risk of KS development.

Acquired Immunodeficiency Syndrome↗