Molecular action of new immunosuppressive agents

Hippokratia 1998, 2(4):147-156

G Vergoulas

Abstract

In kidney transplantation the ultimate target is "intelligent immunosuppression" where we look at each patient and ask whether he is going to be high or low responder to the transplant, whether he needs mono, double, triple or quadruple induction therapy. Our aim is to avoid rejection but at the same time to avoid life threatening infection and malignancy by over immunosuppression, to establish the correct drug dosage, to reduce or stop steroids whenever possible and to minimize side - effects. To do that we need to know about the immunogenetic make-up of the recipient and the mode of action of the drugs concerned.The last forty years there was plenty of time for somebody to get used with an immunosuppressive agent until the appearance of a new one. Now this is not valid. The last few years many new immunosuppressive agents have appeared and are in the final clinical testing or have been approved for clinical use. The development of these new drugs represents a trend for more specific immunosuppression. None of the new drugs has as target the fall of the number of white blood cells and their action targets the function mainly of ? lymphocytes which have been proved to play a central role in the specific immune response of the acute allograft rejection. The new immunosuppressive agents are drugs that either bind with cytoplasmic immunophilines (eg tacrolimus and sirolimus), block purine biosynthesis (mycophenolate mofetil) or finally are antibodies (chimeric and hummanized ) that bind with the IL-2 receptor.

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Screening and early diagnosis of colon cancer

Hippokratia 1998, 2(4):157-164

I. Agorastos

Abstract

Colorectal cancer is a major cause of significant morbidity and mortality. Evidence exists that reductions in colorectal cancer mortality can be achieved through detection and treatment of early-stage colorectal cancers and identification and removal of adenomatous polyps, the precursor to these cancers. Screening tests for colorectal cancer, fecal occult blood tests, sigmoidoscopy, colonoscopy and double contrast barium enema, in asymptomatic individuals in the general population, age 50, have reported a decrease in mortality. Colorectal cancer screening strategies are in an acceptable cost-effectiveness range and are similar to screening mammography; costs can be further reduced by longer intervals and by further genetic research that may identify more high-risk patients to target. At the present time people need to be encouraged to take advantage of and derive benefit from currently available screening strategies in order to reduce their probability of dying from colorectal cancer.

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Orlistat: a new approach to weight control in obese subjects

Hippokratia 1998, 2(4):165-173

D. Panidis, A. Kourtis

Abstract

Gastric and pancreatic lipases are enzymes that play a pivotal role in the digestion of dietary fat. Orlistat, a semi-synthetic derivative of lipstatin, is a potent and selective inhibitor of these enzymes with little or no activity against amylase, trypsin, chymotrypsin and phospholipases. It exerts its effect within the gastrointestinal tract. Orlistat acts by binding covaientiy to the serin residue of the active site of gastric and pancreatic lipases. When administered with fat containing foods, orlistat partially inhibits hydrolysis of triglycerides, thus reducing the subsequent absorption of monoacyl glycerides and free fatty acids. This effect can be measured using 24h fecal fat excretion as a representative pharmacodynamic parameter, orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight gain in obese patients over a 2-year period. The use of orlistat beyond two years needs careful monitoring with respect to efficacy and adverse events.

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Thyroid status in nonthyroidal illness (NTI): hamatologic malignancies

Hippokratia 1998, 2(4):174-178

R. Tsitamidou, Z. Foka, N. Ignatova, N. Tourlas, T Giti

Abstract

Patients with nonthyroidal illness (NTI) but without any apparent underlying thyroid disease often display abnormal values of thyroid hormones. These alterations include low, normal or increased serum T4, reduced T3, normal or low TSH levels. The NTI may affect the hypothala-mus-pituitary-thyroid axis. Evaluation is further complicated by changes in nutrition and effects of medication. The aim of the study was to investigate the prevalence of abnormalities in thyroid assessment tests in patients suffering from hematologic malignancies.The patients (59) were divided according to their therapy (first diagnosis, marrow transplantation, conventional chemotherapy-therapy with interleukin-2 and with GVHD). Serum T3, FT4 and TSH (chemiluninescence method) were assayed. 31% of patients showed biochemical signs of thyroid dysfunction and the remaining pts were euthyroid. These abnormalities will be nonspecific, transient and secondary.
We present a case report of a large epidermoid cyst of the larynx which was removed with direct laryngoscopy from an adult male patient complaining of dysphagia and hoarseness without dyspnea, for an over two month period. The interest in this case is on the large size and rare location of the cyst at the supraglottic region of the larynx, thus causing dysphagia and hoarseness without dyspnea.

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Chronic hepatitis C: Autoantibodies and their correlation to HCV genotype and viraemia

Hippokratia 1998, 2(4):179-182

A. Karantana, Z. Tsimtsiou, E. Giza, S. Christodoulou, A. Lita, I. Mavroudi, E. Orfanou, M. Raptopoulou - Gigi

Abstract
Infection with hepatitis C virus has been found to enhance autoimmune responses and is associated with the presence of various autoantibodies in serum. This study was scheduled in order to investigate the correlation of serum autoantibodies to HCV genotype and viremia. Twenty-six patients with a mean age of 34.2 years participated in the study. The following parameters were tested: ANA, ???, ASMA (indirect immunofluorescence Hep-2), anti-LKM-1(ELISA), Sm, Sm/RNP, SSA, SSB, Jo-1 and Scl 70 (ELISA), cryoglobulins (qualitative assessment), HCV-RNA (quantitative PCR), HCV genotype (INNOLIPA). Our findings showed that 8 patients (30.76%) had positive ANA, 6 had ??? (23.08%), ASMA 1(3,85%), SSA 1(3,85%), SSB 2(7,69%), Sm 2(7,69%), Sm/RNP 2(7,69%) and cryoglobulins 2(7,69%). The anti-LKM-1 was not detected in any of the patients. The most common genotype was found to be 3a; this is probably due to the fact that most patients were ex-drug addicts. No correlation among positive autoantibodies and HCV genotype or viral load was noticed. These results suggest that hepatitis C virus per se induces autoimmune responses and that the enhancement of these responses is not directly related to the genotype or the levels of HCVRNA.

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Large epidermoid cyst of the larynx

Hippokratia 1998, 2(4):183-185

J. Xanthopoulos, G. Nousios, N. Benis, P. Papadopoulos, D. Asimakopoulos, T. Apostolidis

Abstract

We present a case report of a large epidermoid cyst of the larynx which was removed with direct laryngoscopy from an adult male patient complaining of dysphagia and hoarseness without dyspnea, for an over two month period. The interest in this case is on the large size and rare location of the cyst at the supraglottic region of the larynx, thus causing dysphagia and hoarseness without dyspnea.

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Ki-1 (CD 30) Anaplastic large cell lymphoma with extensive eosinophilic infiltration

Hippokratia 2(4):186-188

I.D. Venizelos, M. Leontsini

Abstract

Ki-1 positive anaplastic large - cell malignant lymphoma (Ki-1 ALCL) is an uncommon type of non - Hodgkin' lymphoma. Recently, a morphological subtype of Ki-1 ALCL was described which is characterized by extensive eosinophilic infitration in the absence of necrosis. We describe the clinicopathological features of one case of Ki-1 ALCL, in a 17 year old boy, in which there was extensive infiltration by eosinophils in the absence of necrosis.

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