Post-prandial serum hyaluronan concentration in patients with chronic liver disease

Serum hyaluronan measurement is an option for diagnosing cirrhosis and assessing liver fibrosis, but it is of little use in the diagnosis of chronic hepatitis and compensated liver cirrhosis. It is generally known that intake of food results in elevation of the serum hyaluronan concentration. This work was designed to determine whether a change in the serum hyaluronan concentration after eating might reflect the hepatic sinusoidal endothelial cell impairment in chronic liver diseases. The chronological measurement of serum hyaluronan concentration after eating was performed after an overnight fast in 31 patients with chronic hepatitis, 31 cirrhotic patients, and 8 healthy subjects. The hyaluronan concentration in the loading test increased with the severity of the liver disease in the patients with chronic hepatitis, being significantly higher in the patients with moderate or a higher grade of necroinflammation than in those with a minimal grade, and also significantly higher in patients with stage 3 fibrosis than in those with stage 2 or less. The elevation of the concentration after eating in patients with liver cirrhosis was marked and the range did not overlap with that in patients with chronic hepatitis. Even in 14 patients with compensated liver cirrhosis whose hyaluronan concentration pre-prandially was less than 200 ng/ml, the range of the post-prandial peak concentration did not overlap with that in the chronic hepatitis patients. These results suggest that the evaluation of post-prandial serum hyaluronan concentration is potentially useful for assessing the grading of necroinflammation and staging of fibrosis in patients with chronic hepatitis, as well as for diagnosing compensated liver cirrhosis.     

Prevalence of specific thrombotic accidents in patients with thrombocytosis

The prevalence of specific thrombotic accidents recognized in 260 patients with thrombocytosis are reported. Ninety one were affected by PV, 86 by ET, 20 by MF and 63 by ST. The highest incidence of thrombosis was in the PV group. About half of ET and MF patients experienced a thrombosis. In all the patients thrombosis preferentially affected the cerebrovascular district (17.3% of the cases). Coronary artery disease occurred in PV while peripheral vascular disease was frequent in ET. Portal vein district thrombosis is not rare during the course of all MPD (7.1%). Apparently, deep vein thrombosis occurs in all patients with both primary and secondary thrombocytosis.     

Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease

Kawasaki disease (KD) is an acute systemic vasculitis causing coronary arterial aneurysms and myocardial infarction in young children. Prominent thrombocytosis with increased megakaryocytes develops during the convalescent period. To clarify the mechanisms of thrombocytosis, we studied serum levels of thrombopoietin (TPO) and other thrombopoietic cytokines in 40 patients with KD (149 samples) and 106 age-matched controls using ELISA. TPO values in the controls were 1.94 +/- 0.69 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85 to 3.27 fmol/ml. In the first week of KD, platelet counts were normal but TPO values increased (approximately 15.5 fmol/ml). TPO levels peaked on day 6 +/- 2 at 5.94 +/- 2.64 fmol/ml and then fell gradually. When platelet counts peaked in the second to third weeks, TPO levels were still high or comparable with the controls. TPO levels in KD patients with normal platelet counts were significantly higher than control levels. Interleukin (IL)-6 levels in the first week rose, but neither IL-11 nor leukemia inhibitory factor was detectable. These results suggest that TPO contributes to thrombocytosis in KD in conjunction with IL-6 and TPO production may be enhanced during the acute phase.     

The prognostic value of thrombocytosis in patients with primary lung cancer

The prognostic information provided by platelet counts was studied in 1115 patients with primary lung cancer and in 550 control patients with benign lung disorders. Patient records were retrospectively reviewed regarding histological tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was 32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage (p < 0.0001). Patients with thrombocytosis had a shorter survival than patients with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001). The platelet count and the frequency of thrombocytosis declined after tumour resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism. In conclusion, thrombocytosis is a clinically significant prognostic indicator regarding survival in patients with primary lung cancer.     

Cerebrospinal fluid findings in asymptomatic patients with reactive serum fluorescent treponemal antibody absorption tests

It is common to examine the cerebrospinal fluid in untreated or inadequately treated asymptomatic patients with a reactive serum fluorescent treponemal antibody absorption (FTA-ABS) test before initiating antibiotic therapy for syphilis. This prospective study evaluated the usefulness of such examination. Four hundred thirty-two patients over 40 years old, reporting for annual physical examination, had a serum FTA-ABS test. Thirty-seven (8.6%) patients and 2 of 4 spouses were reactive repeatedly. Of the 39 patients with reactive tests, 7 had a history of penicillin therapy for syphilis, 5 had received heavy metal therapy, and 27 had no history of syphilis. These 39 patients had a neurological examination, serum VDRL, Treponema pallidum immobilization (TPI), and repeat FTA-ABS tests by two other laboratories. The TPI test was reactive in 30 (77%). Four had nonspecific neurological signs. Routine CSF examination (cells, total protein, VDRL, glucose, IgG%) on 30 patients with a history of inadequate treatment had a low diagnostic yield. Two patients had an unexplained total protein elevation (57 and 61 mg/dl) and 1 had a mildly increased IgG% (15%). All cell counts, VDRL tests, and glucose levels were normal. Agarose electrophoresis demonstrated one or more CSF immunoglobulin bands in 10 (36%) of 28 patients, possibly representing an immunological marker of past or latent central nervous system infection.     

Prostaglandin D synthase concentration in cerebrospinal fluid and serum of patients with neurological disorders

Prostaglandin D synthase (PGD synthase) or beta-trace protein is a major constituent of human cerebrospinal fluid (CSF) representing-3% of the total CSF protein. We have recently developed a highly specific immunofluorometric assay for PGD synthase, which enabled us to quantify the presence of PGD synthase in fluids and tissues not associated with the CNS. In this report we provide quantitative data of the presence of PGD synthase in CSF and serum from 302 subjects with various neurological diseases and symptoms. PGD synthase levels in CSF are approximately 35-fold higher than those of serum, with a median concentration of 11,299 micrograms/L. A statistically significant association of PGD synthase concentration in CSF was observed with both patient age and gender. There was no correlation between PGD synthase concentration in serum and patient age or gender. To evaluate the clinical utility of PGD synthase in diagnosing neurological diseases, the distribution pattern of PGD synthase in CSF and serum was examined for each neuropathology of 268 patients whose diagnosis was known. No statistical difference was observed between PGD synthase concentration in the CSF (129 cases) or the serum (94 cases) of multiple sclerosis afflicted subjects in comparison to all other patients studied. The distribution pattern was also not different for PGD synthase levels in CSF of patients with HIV/AIDS related neuropathies, viral meningitis and fibromyalgia. We conclude that PGD synthase measurement presents no clinical utility in diagnosing neurological disorders in adulthood. PGD synthase may have a physiological and/or pathological role in the developing brain and in neurodegenerative diseases.     

Study of serum 3,5,3''-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness

The thyroid doses received by the juvenile population of Belarus following the Chernobyl accident ranged up to about 10 Gy. The thyroid cancer risk estimate recommended in NCRP Report No. 80 was used to predict the number of thyroid cancer cases among children during 1990-1992 in selected Belarussian regions and cities. The results obtained using this risk estimate show an excess of thyroid cancer cases being registered vs. the predicted cases. Thyroid cancer incidence rate among boys under investigation is higher than among girls in the postaccident period. The excess of the observed over the expected incidence in the general juvenile population is caused by the high thyroid cancer incidence rate among boys. These results, which can be considered part of the first stage of a thorough thyroid cancer risk estimation after the Chernobyl accident, demonstrate the critical need to complete these studies in depth.     

The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia

Haloperidol is the most commonly used antipsychotic drug in the therapy of acute schizophrenia. Clinicians have been using therapeutic drug monitoring in an attempt to improve clinical application of this drug. The scale of interest in this area is emphasised by the large number of studies (about 50) concerning the serum concentration-therapeutic effect relationship (SCTER) of haloperidol, including 35 studies on patients with acute schizophrenia. However, conflicting results concerning the existence and position of a therapeutic window have emerged. This article aims to provide a comprehensive review of the study design of studies in patients with acute schizophrenia before the study data are used for decision-making. For this purpose, a reproducible system for the evaluation of studies in this special area, a so-called total study score (TSS), was developed on an empirical basis. Thus, insufficient study design was found to be a reason for negative results. On the other hand, in spite of a great variability, the majority of studies with good design provided evidence for a significant SCTER: a bisigmoidal dependence of clinical effect on haloperidol serum concentration. The therapeutic effects of haloperidol increase at low concentrations, and the concentration has a maximum effect at about 10 micrograms/L and again decreasing at higher concentrations. The data of 552 patients also fit to this model in a single scatter plot (pseudo-r2 = 0.076, p < 0.001). The position of the therapeutic window was determined at about 5.6 to 16.9 micrograms/L. Patients treated with serum concentrations within this optimal range had a significantly better response compared with outside this range (p < 0.001, Student t-test). Therefore, a quantitative synthesis of all available data by means of effect-size analysis provides a mean effect-size (g) = 0.499 +/- 0.182 (standard deviation) for the comparison of haloperidol-treatment with serum concentrations within versus outside the therapeutic window. Thus, because of this moderate positive effect, serum concentration assay of haloperidol is recommended for patients with acute schizophrenia in a therapeutic drug monitoring programme. The modalities of haloperidol therapeutic drug monitoring in clinical practice are discussed, e.g. patient selection, method and time for serum concentration measurement, influence of premedication and comedication, interpretation of results and dose adjustment. Clinical investigations into this subject should focus on covariates which are responsible for the variability of the SCTER. Serum concentration assay is advised for investigations of nonresponse to exclude patients with pseudo-drug resistance.     

Increased serum concentration of soluble CD30 in patients with Graves' disease and Hashimoto's thyroiditis

This study investigated serum levels of the soluble form of CD30 (sCD30), which is mainly secreted from T helper 2(Th2) cells, in autoimmune thyroid diseases. The possible relationship of sCD30 to autoantibody production was also evaluated. Serum levels of sCD30 were determined by an enzyme-linked immunosorbent assay in 71 patients with Graves' disease, 37 patients with Hashimoto's thyroiditis, and 21 normal donors. Compared with normal subjects (7.1 +/- 4.5 U/mL), sCD30 was increased in patients with Graves' disease (29.2 +/- 25.2 U/mL, P < 0.0001) and in patients with Hashimoto's thyroiditis (29.9 +/- 26.9 U/mL, P < 0.0001). In Graves' disease, sCD30 levels were higher in thyrotoxic patients (41.7 +/- 31.2 U/mL, P < 0.001) than in remission patients (15.8 +/- 11.0 U/mL), and a significant correlation was observed between sCD30 levels and serum activities of TSH receptor antibody (r = 0.444, P < 0.0001). In Hashimoto's thyroiditis, sCD30 levels were higher in patients with transient destructive thyrotoxicosis caused by the aggravation of the disease (48.8 +/- 34.4 U/mL, P < 0.05) than in euthyroid patients (24.2 +/- 19.4 U/mL). These data suggest that serum sCD30 is a valuable marker of disease activity and support an important role of the Th2-type immune response in the pathogenesis in Graves' disease and Hashimoto's thyroiditis.     

The relationship between concentration of growth hormone in serum and microangiopathy in patients with diabetes mellitus

OBJECTIVE: To study the relationship between growth hormone (GH) and microangiopathy in patients with diabetes mellitus in order to elucidate pathogenesis on microangiopathy in diabetics. METHODS: GH and insulin (INS) were detected by rdioimmunoassay, and blood sugar (BS) was detected by oxydase method. RESULTS: 138 NIDDM diabetics were examined. The concentration of serum GH in diabetics without microangiopathy (2.3 +/- 1.2 micrograms/L) was higher than in normal people (1.0 +/- 1.2 micrograms/L) and GH in diabetics with microangiopathy (5.74 +/- 1.94 micrograms/L) was higher than in diabetics without microangiopathy. The differences were significant (P < 0.01). As the history of diabetes went on, the level of GH in serum increased, and the incidence of microangiopathy increased too. The correlation of GH in serum with BS was parallel. The correlation of GH in serum with INS was not apparent. 27 ID-DM diabetics were examined, their level of GH in serum (6.8 +/- 3.4 micrograms/L) was higher than that of NIDDM diabetics (4.6 +/- 1.8 micrograms/L). They were all patients with microangiopathy. CONCLUSION: The rise of GH in serum may be an important pathogeny that causes microangiopathy in diabetics.     

Extensive thrombophlebitis with reactive thrombocytosis in a high risk Chinese parturient associated with retained placenta increta: a case report

Forty-three patients with spastic quadriplegia (mean age 7.9 years, range 3.3 to 17.2 years) underwent bone mineral density (BMD) measurement of the lumbar spine and were evaluated between 2.6 and 5.5 years (mean 3.8) later to determine whether this measurement had predicted risk of fracture over the subsequent period of observation. Other potential risk factors that were evaluated include body weight z score, serum vitamin D levels, previous fracture, and hip spica casting. The baseline measurements showed that BMD falls further below normal with increasing age and was more than one standard deviation below age-matched normal mean in 38 of the 43 patients. Fracture rate did not differ between those with low and those with very low spinal BMD. Similarly, serum vitamin D levels and body weight z scores were not predictive of fracture. However, fracture rate was over fourfold greater following spica casting and more than threefold greater following an initial fracture. Fracture rates in the study group were similar to those reported for age- and sex-matched normal children, though generally the location of the fractures and mechanisms of injury differed.     

Splenic irradiation in the palliation of patients with lymphoproliferative and myeloproliferative disorders

INTRODUCTION: Splenic irradiation is an accepted mode of treatment for palliation of hypersplenism and splenic pain for patients with lymphoproliferative or myeloproliferative disorders. However, results are conflicting regarding the duration of palliation and the toxicity associated with this treatment. METHODS: Twenty-five patients with lymphoproliferative or myeloproliferative disorders were treated with splenic irradiation for palliation of splenomegaly and pain. The spleen was measured and pain and toxicity were assessed during radiation therapy. RESULTS: Splenomegaly and splenic pain decreased in 60 percent and 91 percent of patients, respectively. Radiation doses higher than 500 cGy appeared to be more effective than lower doses in reducing the spleen size in patients with chronic lymphocytic leukemia. Regression of splenomegaly and pain relief were maintained for less than one year and more than six months, respectively. Acute radiation toxicity resulted in the cessation of radiotherapy in two patients. CONCLUSION: Splenic irradiation is effective in the short-term palliation of splenomegaly and pain and may be most useful in the subset of patients with a life expectancy of less than one year. Terminally ill patients with splenomegaly secondary to lymphoproliferative or myeloproliferative disorders may benefit from splenic irradiation to minimize pain and pressure symptoms in addition to possible reduction of narcotic use.     

Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis

PURPOSE: Drug free and drug loaded protein-free low density lipoprotein (LDL) models consisting mainly of phospholipids, cholesterol, cholesterol esters, and triglycerides in ratios found for physiological LDL have been prepared. Their physicochemical characteristics were compared with those of physiological LDL. METHODS: Different characterization methods were used: photon correlation spectroscopy, transmission electron microscopy, X-ray solution scattering, and 1H nuclear magnetic resonance spectroscopy (NMR). RESULTS: Particle sizes are highly dependent on the preparation method and in particular on the homogenization conditions. Electron microscopy indicates that the size distributions of model systems are much broader than those of physiological LDL. The X-ray solution scattering patterns of the model systems display a temperature dependent maximum near 3.8 nm similar to that found in the patterns of physiological LDL. NMR indicates a comparable mobility of the lipid molecules in model particles and in physiological LDL. The influence of drug loading is similar to that found earlier for physiological LDL. In particular, the incorporation of the anti-cancer drug WB 4291 seems to have a fluidizing effect on the lipids in the core region of the particles. CONCLUSIONS: The preparation method of LDL model systems is of crucial importance as only the solvent evaporation method yielded systems in the size range of physiological LDL with acceptable high lipid concentrations. The fluidizing influence of temperature and drug incorporation (WB 4291) may be disadvantage in drug targeting.     

The relationship of the theophylline concentration in the saliva and the blood serum in patients with a broncho-obstructive syndrome

Theophylline salivary and serum concentrations (Tser and Tsal) were quantified after a single dose administration of theophylline drugs: euphylline (2.4% solution, 10 ml i.v. jet and 0.15 orally), theo-dur, retaphil, theopek, theobilong (0.3 g orally). The drugs were given to patients with broncho-obstructive syndrome. The samples were obtained within 6 and 24 hours upon administration for euphylline and other drugs, respectively. Tser and Tsal were determined at high-performance liquid chromatography. The authors revealed a linear relationship between Tser and Tsal in different time intervals. The percentage factors and formulas of Tser calculation by its Tsal values have been estimated.     

Elevated ganglioside concentration in serum and peripheral blood lymphocytes from multiple sclerosis patients in remission

The ganglioside concentration in pooled serum from 20 patients with clinically definite multiple sclerosis (MS) was determined and compared with that in pooled serum from a similar number of healthy blood donors. There as a significant increase in the concentration of ganglioside-bound sialic acid from 691 +/- 57 micrograms/100 ml in the control sera to 926 +/-m 83 micrograms 100 ml in MS patients' sera. The profile of individual gangliosides in the two groups was identical, the four main structures being GM3, GD3, and GD1a and GT1b. The ganglioside pattern and concentration in peripheral blood lymphocytes derived from MS patients and controls was identical with the predominant GM3, and small proportions of Gd3. MS lymphocytes also showed a 39% increase in ganglioside content over control lymphocytes. The implication of such pronounced ganglioside increases is discussed with regard to the impaired immunocompetence of lymphocytes reported in MS.     

Comparative concentration of serum free amino acids in patients with incipient and manifest organic neuropsychiatric disorders of vascular origin

The authors conducted a study of the quantitative content of amino acids in the blood serum of patients with initial and expressed organic neuro-psychic disorders of a vascular genesis and in a group of normals of the same age. In patients with initial organic syndromes the content of cystin-cystein and treonine in the blood serum increased. In patients with expressed organic syndromes the content of cystin-cystein increased, while the content of arginine acid and leicyn-isoleicyn decreased as compared to the control group of elderly people. A comparative study of the two groups of patients with organic psychopathology of a vascular origin demonstrated that in vascular dementia there are more severe changes in the content of amino acids in the blood serum.     

Apolipoprotein(a) genetic polymorphism and serum lipoprotein(a) concentration in patients with peripheral vascular disease

Serum lipoprotein(a) (Lp(a)) levels were measured in 89 men with peripheral vascular disease (PVD) and 129 (100 male and 29 woman) healthy controls. Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in all subjects. Patients with PVD had significantly higher serum Lp(a) levels than controls. Apolipoprotein(a) phenotype frequencies in patients with PVD did not differ from those of the control group. Both patients and controls with phenotype S2 had higher serum Lp(a) levels than those with phenotype S4. It should be emphasized that serum Lp(a) levels were significantly higher in PVD patients than controls for those with phenotype S2, S3/S4 and S4. Raised serum Lp(a) levels together with other lipoprotein abnormalities in patients with PVD imply a high cardiovascular risk. Genetic polymorphism clearly influences serum Lp(a) levels both in patients and controls. In patients with PVD, environmental and/or other genetic factors must play a role in raising Lp(a) levels.     

Familial thrombocytosis in infancy presenting with a leukaemoid reaction

Familial thrombocytosis (FT) is a hereditary disorder probably involving the regulation of megakaryopoiesis. This report is the first documented case of FT in infancy. The clinical course was complicated by a leukaemoid reaction which lasted for several months, in combination with failure to thrive and hepatosplenomegaly. At the age of 5 years the patient, with the exception of thrombocytosis, is healthy and without medication.